<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with Wdesk from Workiva-->
<!--Copyright 2021 Workiva-->
<!--r:83f390d0-6781-4e7e-a1f5-5192701136a4,g:3039e280-7bbd-437e-b91e-6280679dfdce-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:roleRef roleURI="http://www.lilly.com/role/ConsolidatedCondensedStatementsofOperations" xlink:type="simple" xlink:href="lly-20210930.xsd#ConsolidatedCondensedStatementsofOperations"/>
  <link:calculationLink xlink:role="http://www.lilly.com/role/ConsolidatedCondensedStatementsofOperations" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_lly_CostOfSalesOperatingExpensesAndOtherNet_01ac8b55-ef25-486c-bdd1-448c6e9bebea" xlink:href="lly-20210930.xsd#lly_CostOfSalesOperatingExpensesAndOtherNet"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSold_e22942a8-68ac-4b59-86a0-408ae7e6e77a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostOfGoodsAndServicesSold"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_lly_CostOfSalesOperatingExpensesAndOtherNet_01ac8b55-ef25-486c-bdd1-448c6e9bebea" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSold_e22942a8-68ac-4b59-86a0-408ae7e6e77a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_b3cf4398-ff53-4280-8024-0cad2c42453c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_lly_CostOfSalesOperatingExpensesAndOtherNet_01ac8b55-ef25-486c-bdd1-448c6e9bebea" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_b3cf4398-ff53-4280-8024-0cad2c42453c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpense_a6667375-9943-46cf-8a0a-95d463eee089" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SellingGeneralAndAdministrativeExpense"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_lly_CostOfSalesOperatingExpensesAndOtherNet_01ac8b55-ef25-486c-bdd1-448c6e9bebea" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpense_a6667375-9943-46cf-8a0a-95d463eee089" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lly_AcquiredInProcessResearchAndDevelopment_98bcf335-a23a-48f6-a629-0bd417c63235" xlink:href="lly-20210930.xsd#lly_AcquiredInProcessResearchAndDevelopment"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_lly_CostOfSalesOperatingExpensesAndOtherNet_01ac8b55-ef25-486c-bdd1-448c6e9bebea" xlink:to="loc_lly_AcquiredInProcessResearchAndDevelopment_98bcf335-a23a-48f6-a629-0bd417c63235" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringSettlementAndImpairmentProvisions_eda75cc2-b3b1-49ee-abc8-c993eb9f96ea" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestructuringSettlementAndImpairmentProvisions"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_lly_CostOfSalesOperatingExpensesAndOtherNet_01ac8b55-ef25-486c-bdd1-448c6e9bebea" xlink:to="loc_us-gaap_RestructuringSettlementAndImpairmentProvisions_eda75cc2-b3b1-49ee-abc8-c993eb9f96ea" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonoperatingIncomeExpense_13da9152-e357-4a74-8993-c4d07a82b65a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NonoperatingIncomeExpense"/>
    <link:calculationArc order="6" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_lly_CostOfSalesOperatingExpensesAndOtherNet_01ac8b55-ef25-486c-bdd1-448c6e9bebea" xlink:to="loc_us-gaap_NonoperatingIncomeExpense_13da9152-e357-4a74-8993-c4d07a82b65a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_64bd7074-62cc-4cb7-a620-83128c884cf2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_b07f83b5-1e7f-43b2-9fba-5d75e62fb0a3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Revenues"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_64bd7074-62cc-4cb7-a620-83128c884cf2" xlink:to="loc_us-gaap_Revenues_b07f83b5-1e7f-43b2-9fba-5d75e62fb0a3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lly_CostOfSalesOperatingExpensesAndOtherNet_250f0324-df80-4d3c-9bb9-32d0e6f9b5d4" xlink:href="lly-20210930.xsd#lly_CostOfSalesOperatingExpensesAndOtherNet"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_64bd7074-62cc-4cb7-a620-83128c884cf2" xlink:to="loc_lly_CostOfSalesOperatingExpensesAndOtherNet_250f0324-df80-4d3c-9bb9-32d0e6f9b5d4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_d8faaee1-9f48-4c18-8c06-ec256bbe1682" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_f933b8e9-2931-4cc2-a669-5138e3c9c8ce" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_d8faaee1-9f48-4c18-8c06-ec256bbe1682" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_f933b8e9-2931-4cc2-a669-5138e3c9c8ce" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_8b99369a-da3d-4e6a-81dc-5774b691124e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_d8faaee1-9f48-4c18-8c06-ec256bbe1682" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_8b99369a-da3d-4e6a-81dc-5774b691124e" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.lilly.com/role/ConsolidatedCondensedStatementsofComprehensiveIncomeLoss" xlink:type="simple" xlink:href="lly-20210930.xsd#ConsolidatedCondensedStatementsofComprehensiveIncomeLoss"/>
  <link:calculationLink xlink:role="http://www.lilly.com/role/ConsolidatedCondensedStatementsofComprehensiveIncomeLoss" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomeNetOfTax_893ce876-d0b0-47a6-bca7-5de621ac9d27" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTax"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTax_db4ffe5c-1e2f-4e73-af34-352d389882c8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_893ce876-d0b0-47a6-bca7-5de621ac9d27" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTax_db4ffe5c-1e2f-4e73-af34-352d389882c8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_3c169d26-da2b-4572-a976-8e75b300cae2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_893ce876-d0b0-47a6-bca7-5de621ac9d27" xlink:to="loc_us-gaap_NetIncomeLoss_3c169d26-da2b-4572-a976-8e75b300cae2" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.lilly.com/role/ConsolidatedCondensedBalanceSheets" xlink:type="simple" xlink:href="lly-20210930.xsd#ConsolidatedCondensedBalanceSheets"/>
  <link:calculationLink xlink:role="http://www.lilly.com/role/ConsolidatedCondensedBalanceSheets" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_8c8cfcc8-88e9-4bad-9b6e-e689b5ffd4b4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockValue_0d507038-cf2a-4fdc-9e11-9d37b65e405d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_8c8cfcc8-88e9-4bad-9b6e-e689b5ffd4b4" xlink:to="loc_us-gaap_CommonStockValue_0d507038-cf2a-4fdc-9e11-9d37b65e405d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalCommonStock_d69f530c-52b8-40cb-bdb8-e32e16957f33" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdditionalPaidInCapitalCommonStock"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_8c8cfcc8-88e9-4bad-9b6e-e689b5ffd4b4" xlink:to="loc_us-gaap_AdditionalPaidInCapitalCommonStock_d69f530c-52b8-40cb-bdb8-e32e16957f33" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsAccumulatedDeficit_86f177b4-5dd2-4bb6-8912-29dd97b65aa9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_8c8cfcc8-88e9-4bad-9b6e-e689b5ffd4b4" xlink:to="loc_us-gaap_RetainedEarningsAccumulatedDeficit_86f177b4-5dd2-4bb6-8912-29dd97b65aa9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesHeldInEmployeeTrust_885315b7-6bc0-4a5d-9882-1fc8d7655411" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockSharesHeldInEmployeeTrust"/>
    <link:calculationArc order="4" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_8c8cfcc8-88e9-4bad-9b6e-e689b5ffd4b4" xlink:to="loc_us-gaap_CommonStockSharesHeldInEmployeeTrust_885315b7-6bc0-4a5d-9882-1fc8d7655411" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_ae044e31-6f4f-4564-bd61-24a6f540aee7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_8c8cfcc8-88e9-4bad-9b6e-e689b5ffd4b4" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_ae044e31-6f4f-4564-bd61-24a6f540aee7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TreasuryStockValue_f92c4149-e5e5-4bfe-a946-3a7606df702d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TreasuryStockValue"/>
    <link:calculationArc order="6" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_8c8cfcc8-88e9-4bad-9b6e-e689b5ffd4b4" xlink:to="loc_us-gaap_TreasuryStockValue_f92c4149-e5e5-4bfe-a946-3a7606df702d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_ee6ca597-90e1-49ca-a106-855defed04b9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsPayableCurrent_7c590636-9f84-4af2-92c3-092ba0e1f91a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsPayableCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_ee6ca597-90e1-49ca-a106-855defed04b9" xlink:to="loc_us-gaap_AccountsPayableCurrent_7c590636-9f84-4af2-92c3-092ba0e1f91a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeRelatedLiabilitiesCurrent_a0bce2bd-9ff6-43e2-9993-df3280f9cd4a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_ee6ca597-90e1-49ca-a106-855defed04b9" xlink:to="loc_us-gaap_EmployeeRelatedLiabilitiesCurrent_a0bce2bd-9ff6-43e2-9993-df3280f9cd4a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lly_SalesRebatesAndDiscounts_4c05ea56-e06b-40d1-8f5e-5be8cc34718e" xlink:href="lly-20210930.xsd#lly_SalesRebatesAndDiscounts"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_ee6ca597-90e1-49ca-a106-855defed04b9" xlink:to="loc_lly_SalesRebatesAndDiscounts_4c05ea56-e06b-40d1-8f5e-5be8cc34718e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DividendsPayableCurrent_9bacc4b8-d032-4581-9cf8-a2a43affa710" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DividendsPayableCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_ee6ca597-90e1-49ca-a106-855defed04b9" xlink:to="loc_us-gaap_DividendsPayableCurrent_9bacc4b8-d032-4581-9cf8-a2a43affa710" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TaxesPayableCurrent_32a41448-0a90-4cc2-85ea-155cadc2926d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TaxesPayableCurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_ee6ca597-90e1-49ca-a106-855defed04b9" xlink:to="loc_us-gaap_TaxesPayableCurrent_32a41448-0a90-4cc2-85ea-155cadc2926d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesCurrent_d75911a9-195f-4d83-a954-bf3adbffc80d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherLiabilitiesCurrent"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_ee6ca597-90e1-49ca-a106-855defed04b9" xlink:to="loc_us-gaap_OtherLiabilitiesCurrent_d75911a9-195f-4d83-a954-bf3adbffc80d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtCurrent_cab54634-6ee9-49ea-8372-a4996406cb7b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtCurrent"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_ee6ca597-90e1-49ca-a106-855defed04b9" xlink:to="loc_us-gaap_DebtCurrent_cab54634-6ee9-49ea-8372-a4996406cb7b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_5071cde6-5ef1-43da-a79c-ec7c732234b7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_d8efd829-df53-422d-b411-e136994437a5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquity"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_5071cde6-5ef1-43da-a79c-ec7c732234b7" xlink:to="loc_us-gaap_StockholdersEquity_d8efd829-df53-422d-b411-e136994437a5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MinorityInterest_cbcdc21f-d2be-461a-82e1-91a2334e72d1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MinorityInterest"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_5071cde6-5ef1-43da-a79c-ec7c732234b7" xlink:to="loc_us-gaap_MinorityInterest_cbcdc21f-d2be-461a-82e1-91a2334e72d1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesNoncurrent_630835ed-e491-4ba6-8a5a-9ada77758365" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesNoncurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedIncomeTaxesNoncurrent_61316d14-87b2-4ea4-a8bd-4a4e577ecff1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccruedIncomeTaxesNoncurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesNoncurrent_630835ed-e491-4ba6-8a5a-9ada77758365" xlink:to="loc_us-gaap_AccruedIncomeTaxesNoncurrent_61316d14-87b2-4ea4-a8bd-4a4e577ecff1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtNoncurrent_87b70e60-708d-45a6-989e-1067efce0de5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongTermDebtNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesNoncurrent_630835ed-e491-4ba6-8a5a-9ada77758365" xlink:to="loc_us-gaap_LongTermDebtNoncurrent_87b70e60-708d-45a6-989e-1067efce0de5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PensionAndOtherPostretirementDefinedBenefitPlansLiabilitiesNoncurrent_ed613f39-86e8-4960-8882-cc902b9ab8f3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PensionAndOtherPostretirementDefinedBenefitPlansLiabilitiesNoncurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesNoncurrent_630835ed-e491-4ba6-8a5a-9ada77758365" xlink:to="loc_us-gaap_PensionAndOtherPostretirementDefinedBenefitPlansLiabilitiesNoncurrent_ed613f39-86e8-4960-8882-cc902b9ab8f3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesNoncurrent_9dbecf56-1c9f-459c-8664-f7576aadf22f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherLiabilitiesNoncurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesNoncurrent_630835ed-e491-4ba6-8a5a-9ada77758365" xlink:to="loc_us-gaap_OtherLiabilitiesNoncurrent_9dbecf56-1c9f-459c-8664-f7576aadf22f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncomeTaxLiabilitiesNet_c866a419-121a-4a08-b197-ad777b49bf60" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredIncomeTaxLiabilitiesNet"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesNoncurrent_630835ed-e491-4ba6-8a5a-9ada77758365" xlink:to="loc_us-gaap_DeferredIncomeTaxLiabilitiesNet_c866a419-121a-4a08-b197-ad777b49bf60" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Assets_8a42713c-6ba3-411c-a73e-e02ce9502a4b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Assets"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_83d07d7d-b206-461d-99f2-e07e2975b467" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_8a42713c-6ba3-411c-a73e-e02ce9502a4b" xlink:to="loc_us-gaap_AssetsCurrent_83d07d7d-b206-461d-99f2-e07e2975b467" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermInvestments_82a312dd-1fd3-4dd6-9e65-844ac239b38b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongTermInvestments"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_8a42713c-6ba3-411c-a73e-e02ce9502a4b" xlink:to="loc_us-gaap_LongTermInvestments_82a312dd-1fd3-4dd6-9e65-844ac239b38b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Goodwill_e50323cc-dc2e-47d2-ac65-4b8d21e30c2e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Goodwill"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_8a42713c-6ba3-411c-a73e-e02ce9502a4b" xlink:to="loc_us-gaap_Goodwill_e50323cc-dc2e-47d2-ac65-4b8d21e30c2e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IntangibleAssetsNetExcludingGoodwill_9a9ab57b-5b63-460c-a5f3-6da16d3a69f0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IntangibleAssetsNetExcludingGoodwill"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_8a42713c-6ba3-411c-a73e-e02ce9502a4b" xlink:to="loc_us-gaap_IntangibleAssetsNetExcludingGoodwill_9a9ab57b-5b63-460c-a5f3-6da16d3a69f0" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncomeTaxAssetsNet_94e67225-e0fb-4e4f-9d50-13cd78a05a31" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredIncomeTaxAssetsNet"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_8a42713c-6ba3-411c-a73e-e02ce9502a4b" xlink:to="loc_us-gaap_DeferredIncomeTaxAssetsNet_94e67225-e0fb-4e4f-9d50-13cd78a05a31" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsNoncurrent_85793de7-533e-4f7e-a45a-943c5d83af3f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherAssetsNoncurrent"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_8a42713c-6ba3-411c-a73e-e02ce9502a4b" xlink:to="loc_us-gaap_OtherAssetsNoncurrent_85793de7-533e-4f7e-a45a-943c5d83af3f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_06f440fa-55b6-4a83-a083-d2296011659a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_8a42713c-6ba3-411c-a73e-e02ce9502a4b" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet_06f440fa-55b6-4a83-a083-d2296011659a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_158e6205-cff5-4dff-b439-860c4a8e2ff5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_25040106-82b2-40ba-ac72-0dc583ec2c75" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_158e6205-cff5-4dff-b439-860c4a8e2ff5" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_25040106-82b2-40ba-ac72-0dc583ec2c75" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermInvestments_c325df76-8405-41af-a6d7-e2191120e8c1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShortTermInvestments"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_158e6205-cff5-4dff-b439-860c4a8e2ff5" xlink:to="loc_us-gaap_ShortTermInvestments_c325df76-8405-41af-a6d7-e2191120e8c1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableNetCurrent_26b4edb2-29a9-4ac1-9c70-aab931ff5289" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsReceivableNetCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_158e6205-cff5-4dff-b439-860c4a8e2ff5" xlink:to="loc_us-gaap_AccountsReceivableNetCurrent_26b4edb2-29a9-4ac1-9c70-aab931ff5289" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherReceivablesNetCurrent_1133ebcc-ee2f-4d85-9312-ff3d642aa026" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherReceivablesNetCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_158e6205-cff5-4dff-b439-860c4a8e2ff5" xlink:to="loc_us-gaap_OtherReceivablesNetCurrent_1133ebcc-ee2f-4d85-9312-ff3d642aa026" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryNet_0a496fa0-29d4-4fb9-8b6d-0ff475706b10" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNet"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_158e6205-cff5-4dff-b439-860c4a8e2ff5" xlink:to="loc_us-gaap_InventoryNet_0a496fa0-29d4-4fb9-8b6d-0ff475706b10" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrepaidExpenseCurrent_40320075-675c-4ee3-8262-379b19e6d1d4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PrepaidExpenseCurrent"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_158e6205-cff5-4dff-b439-860c4a8e2ff5" xlink:to="loc_us-gaap_PrepaidExpenseCurrent_40320075-675c-4ee3-8262-379b19e6d1d4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesAndStockholdersEquity_1e072181-429d-422d-965c-7e2d650c2a68" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_a7aa8cb6-5832-407a-9016-83e6adad2c56" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_1e072181-429d-422d-965c-7e2d650c2a68" xlink:to="loc_us-gaap_LiabilitiesCurrent_a7aa8cb6-5832-407a-9016-83e6adad2c56" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesNoncurrent_59cb306f-682b-4ae5-a494-b65193f34e2c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_1e072181-429d-422d-965c-7e2d650c2a68" xlink:to="loc_us-gaap_LiabilitiesNoncurrent_59cb306f-682b-4ae5-a494-b65193f34e2c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_3a60c484-112f-4848-9b87-0685435bdc32" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_1e072181-429d-422d-965c-7e2d650c2a68" xlink:to="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_3a60c484-112f-4848-9b87-0685435bdc32" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommitmentsAndContingencies_13ab3bc4-0d25-4877-87e8-b3076b04d1be" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommitmentsAndContingencies"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_1e072181-429d-422d-965c-7e2d650c2a68" xlink:to="loc_us-gaap_CommitmentsAndContingencies_13ab3bc4-0d25-4877-87e8-b3076b04d1be" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.lilly.com/role/ConsolidatedCondensedStatementsofCashFlows" xlink:type="simple" xlink:href="lly-20210930.xsd#ConsolidatedCondensedStatementsofCashFlows"/>
  <link:calculationLink xlink:role="http://www.lilly.com/role/ConsolidatedCondensedStatementsofCashFlows" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_da94c164-e5b2-4a6f-9901-f613a39666d4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsOfDividends_2ce4366a-f07d-46e7-b87a-7404a61430e4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsOfDividends"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_da94c164-e5b2-4a6f-9901-f613a39666d4" xlink:to="loc_us-gaap_PaymentsOfDividends_2ce4366a-f07d-46e7-b87a-7404a61430e4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepaymentsOfLongTermDebt_0b119386-046c-44f9-8e93-66fb5173da5d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RepaymentsOfLongTermDebt"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_da94c164-e5b2-4a6f-9901-f613a39666d4" xlink:to="loc_us-gaap_RepaymentsOfLongTermDebt_0b119386-046c-44f9-8e93-66fb5173da5d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_b20d96cf-cf46-4483-a49d-ae2142d982b8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsForRepurchaseOfCommonStock"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_da94c164-e5b2-4a6f-9901-f613a39666d4" xlink:to="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_b20d96cf-cf46-4483-a49d-ae2142d982b8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromPaymentsForOtherFinancingActivities_3da19973-9f1f-4611-b1ff-1c04193c8c1b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromPaymentsForOtherFinancingActivities"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_da94c164-e5b2-4a6f-9901-f613a39666d4" xlink:to="loc_us-gaap_ProceedsFromPaymentsForOtherFinancingActivities_3da19973-9f1f-4611-b1ff-1c04193c8c1b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromShortTermDebt_83f9ab8e-9c33-4896-a52d-2fc9249a7053" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromShortTermDebt"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_da94c164-e5b2-4a6f-9901-f613a39666d4" xlink:to="loc_us-gaap_ProceedsFromShortTermDebt_83f9ab8e-9c33-4896-a52d-2fc9249a7053" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepaymentsOfShortTermDebt_fac32026-2984-4d93-9435-69b2e8b9e1f8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RepaymentsOfShortTermDebt"/>
    <link:calculationArc order="6" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_da94c164-e5b2-4a6f-9901-f613a39666d4" xlink:to="loc_us-gaap_RepaymentsOfShortTermDebt_fac32026-2984-4d93-9435-69b2e8b9e1f8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfLongTermDebt_9f51c2b3-b22a-4f13-9a4f-5d1bf1d53149" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceOfLongTermDebt"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_da94c164-e5b2-4a6f-9901-f613a39666d4" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfLongTermDebt_9f51c2b3-b22a-4f13-9a4f-5d1bf1d53149" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_b4547898-ae58-4f36-9c9f-3f8917071c42" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_78b89a6d-0f68-48bb-9be3-2f0f4153443e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_b4547898-ae58-4f36-9c9f-3f8917071c42" xlink:to="loc_us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_78b89a6d-0f68-48bb-9be3-2f0f4153443e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_9ba95c19-5484-4d96-802a-5a5b53b3ffec" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_b4547898-ae58-4f36-9c9f-3f8917071c42" xlink:to="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_9ba95c19-5484-4d96-802a-5a5b53b3ffec" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_6798f809-ce92-4a86-b228-83c0fcbc09d8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_b4547898-ae58-4f36-9c9f-3f8917071c42" xlink:to="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_6798f809-ce92-4a86-b228-83c0fcbc09d8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_ed8b595f-6b5b-421e-9350-efef6e8bda03" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_b4547898-ae58-4f36-9c9f-3f8917071c42" xlink:to="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_ed8b595f-6b5b-421e-9350-efef6e8bda03" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_99334b70-fcf0-4032-b47b-b5813668cd55" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromSaleOfShortTermInvestments_1ba62d41-9a68-4047-8650-48fab283182d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromSaleOfShortTermInvestments"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_99334b70-fcf0-4032-b47b-b5813668cd55" xlink:to="loc_us-gaap_ProceedsFromSaleOfShortTermInvestments_1ba62d41-9a68-4047-8650-48fab283182d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireShortTermInvestments_718eb417-9d7d-49b0-9a5b-7cf2050fcde3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquireShortTermInvestments"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_99334b70-fcf0-4032-b47b-b5813668cd55" xlink:to="loc_us-gaap_PaymentsToAcquireShortTermInvestments_718eb417-9d7d-49b0-9a5b-7cf2050fcde3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromSaleOfLongtermInvestments_d0ec6acb-7c78-4f5e-a3eb-6de648d948f3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromSaleOfLongtermInvestments"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_99334b70-fcf0-4032-b47b-b5813668cd55" xlink:to="loc_us-gaap_ProceedsFromSaleOfLongtermInvestments_d0ec6acb-7c78-4f5e-a3eb-6de648d948f3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForProceedsFromOtherInvestingActivities_958c3c53-e7cf-4f85-8427-b2d3d4cf5963" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsForProceedsFromOtherInvestingActivities"/>
    <link:calculationArc order="4" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_99334b70-fcf0-4032-b47b-b5813668cd55" xlink:to="loc_us-gaap_PaymentsForProceedsFromOtherInvestingActivities_958c3c53-e7cf-4f85-8427-b2d3d4cf5963" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireLongtermInvestments_bd4dba94-087d-4354-8d48-7e57cd24be57" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquireLongtermInvestments"/>
    <link:calculationArc order="5" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_99334b70-fcf0-4032-b47b-b5813668cd55" xlink:to="loc_us-gaap_PaymentsToAcquireLongtermInvestments_bd4dba94-087d-4354-8d48-7e57cd24be57" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lly_PurchasedInProcessResearchAndDevelopment_da1d5a06-8a5d-454f-9609-d9a78b314c7c" xlink:href="lly-20210930.xsd#lly_PurchasedInProcessResearchAndDevelopment"/>
    <link:calculationArc order="6" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_99334b70-fcf0-4032-b47b-b5813668cd55" xlink:to="loc_lly_PurchasedInProcessResearchAndDevelopment_da1d5a06-8a5d-454f-9609-d9a78b314c7c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireBusinessesNetOfCashAcquired_2a852a0e-e628-49fa-a031-e33a9b21a8c9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquireBusinessesNetOfCashAcquired"/>
    <link:calculationArc order="7" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_99334b70-fcf0-4032-b47b-b5813668cd55" xlink:to="loc_us-gaap_PaymentsToAcquireBusinessesNetOfCashAcquired_2a852a0e-e628-49fa-a031-e33a9b21a8c9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireProductiveAssets_dd6bf211-99e6-4324-b3d7-a748b94df142" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquireProductiveAssets"/>
    <link:calculationArc order="8" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_99334b70-fcf0-4032-b47b-b5813668cd55" xlink:to="loc_us-gaap_PaymentsToAcquireProductiveAssets_dd6bf211-99e6-4324-b3d7-a748b94df142" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_01c24c46-39d4-49fe-8c71-8bf55e6db2a6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_21c4ebf3-520e-48e4-8ce4-5bb4e50e18b8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_01c24c46-39d4-49fe-8c71-8bf55e6db2a6" xlink:to="loc_us-gaap_NetIncomeLoss_21c4ebf3-520e-48e4-8ce4-5bb4e50e18b8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DepreciationDepletionAndAmortization_ff0c08b2-bbe4-4d12-8560-b9b744e12665" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DepreciationDepletionAndAmortization"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_01c24c46-39d4-49fe-8c71-8bf55e6db2a6" xlink:to="loc_us-gaap_DepreciationDepletionAndAmortization_ff0c08b2-bbe4-4d12-8560-b9b744e12665" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInDeferredIncomeTaxes_7d7491d8-3f6d-415f-8201-05f85c20d65b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInDeferredIncomeTaxes"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_01c24c46-39d4-49fe-8c71-8bf55e6db2a6" xlink:to="loc_us-gaap_IncreaseDecreaseInDeferredIncomeTaxes_7d7491d8-3f6d-415f-8201-05f85c20d65b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensation_1ceae26c-fde3-42cb-8ae6-05fed26f8243" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensation"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_01c24c46-39d4-49fe-8c71-8bf55e6db2a6" xlink:to="loc_us-gaap_ShareBasedCompensation_1ceae26c-fde3-42cb-8ae6-05fed26f8243" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lly_AcquiredInProcessResearchAndDevelopment_38e9d631-ad4d-461c-9a24-989e921840c9" xlink:href="lly-20210930.xsd#lly_AcquiredInProcessResearchAndDevelopment"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_01c24c46-39d4-49fe-8c71-8bf55e6db2a6" xlink:to="loc_lly_AcquiredInProcessResearchAndDevelopment_38e9d631-ad4d-461c-9a24-989e921840c9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInOtherOperatingCapitalNet_28e3b537-6e1a-43f0-b7e9-b787fb1e8c6d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInOtherOperatingCapitalNet"/>
    <link:calculationArc order="6" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_01c24c46-39d4-49fe-8c71-8bf55e6db2a6" xlink:to="loc_us-gaap_IncreaseDecreaseInOtherOperatingCapitalNet_28e3b537-6e1a-43f0-b7e9-b787fb1e8c6d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherOperatingActivitiesCashFlowStatement_dca37174-36c4-4a0f-a1ec-a98cddcae8e4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherOperatingActivitiesCashFlowStatement"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_01c24c46-39d4-49fe-8c71-8bf55e6db2a6" xlink:to="loc_us-gaap_OtherOperatingActivitiesCashFlowStatement_dca37174-36c4-4a0f-a1ec-a98cddcae8e4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainLossOnInvestments_3fe803da-06ba-49e1-b0ef-d69e346a74fa" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnInvestments"/>
    <link:calculationArc order="8" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_01c24c46-39d4-49fe-8c71-8bf55e6db2a6" xlink:to="loc_us-gaap_GainLossOnInvestments_3fe803da-06ba-49e1-b0ef-d69e346a74fa" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_3a432ff3-4784-4d6d-a532-f9ede565bc94" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainsLossesOnExtinguishmentOfDebt"/>
    <link:calculationArc order="9" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_01c24c46-39d4-49fe-8c71-8bf55e6db2a6" xlink:to="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_3a432ff3-4784-4d6d-a532-f9ede565bc94" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.lilly.com/role/AcquisitionsAssetsAcquiredandLiabilitiesAssumedDetails" xlink:type="simple" xlink:href="lly-20210930.xsd#AcquisitionsAssetsAcquiredandLiabilitiesAssumedDetails"/>
  <link:calculationLink xlink:role="http://www.lilly.com/role/AcquisitionsAssetsAcquiredandLiabilitiesAssumedDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet_1177f6e0-5303-449d-9700-7f51d4d77c24" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIntangibleAssetsOtherThanGoodwill_9fd3c637-b8de-402c-ad86-a9844c0fafcf" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIntangibleAssetsOtherThanGoodwill"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet_1177f6e0-5303-449d-9700-7f51d4d77c24" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIntangibleAssetsOtherThanGoodwill_9fd3c637-b8de-402c-ad86-a9844c0fafcf" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxLiabilities_7c46198a-8f5a-45cb-a70f-c3c697cd7c9d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxLiabilities"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet_1177f6e0-5303-449d-9700-7f51d4d77c24" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxLiabilities_7c46198a-8f5a-45cb-a70f-c3c697cd7c9d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCashAndEquivalents_e094b71a-8f75-4f19-a63f-43cf56791524" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCashAndEquivalents"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet_1177f6e0-5303-449d-9700-7f51d4d77c24" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCashAndEquivalents_e094b71a-8f75-4f19-a63f-43cf56791524" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lly_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherAssetsLiabilitiesNet_fa4e1eb8-8bf8-4801-9360-71e3c69e4cf0" xlink:href="lly-20210930.xsd#lly_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherAssetsLiabilitiesNet"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet_1177f6e0-5303-449d-9700-7f51d4d77c24" xlink:to="loc_lly_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherAssetsLiabilitiesNet_fa4e1eb8-8bf8-4801-9360-71e3c69e4cf0" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Goodwill_767edc59-3d9c-4fb4-bc1b-b5e5d825e40e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Goodwill"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet_1177f6e0-5303-449d-9700-7f51d4d77c24" xlink:to="loc_us-gaap_Goodwill_767edc59-3d9c-4fb4-bc1b-b5e5d825e40e" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.lilly.com/role/AssetImpairmentRestructuringandOtherSpecialChargesDetails" xlink:type="simple" xlink:href="lly-20210930.xsd#AssetImpairmentRestructuringandOtherSpecialChargesDetails"/>
  <link:calculationLink xlink:role="http://www.lilly.com/role/AssetImpairmentRestructuringandOtherSpecialChargesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringSettlementAndImpairmentProvisions_c2fb85bc-493a-41c5-9b20-196b63d2faf3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestructuringSettlementAndImpairmentProvisions"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeveranceCosts1_1c1bc9ec-0d05-4cdc-8109-6ae66d767d90" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SeveranceCosts1"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_RestructuringSettlementAndImpairmentProvisions_c2fb85bc-493a-41c5-9b20-196b63d2faf3" xlink:to="loc_us-gaap_SeveranceCosts1_1c1bc9ec-0d05-4cdc-8109-6ae66d767d90" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lly_AssetImpairmentChargesRecoveriesAndOtherSpecialCharges_cbf58ccb-3ff3-4093-85fd-abf52b2939b0" xlink:href="lly-20210930.xsd#lly_AssetImpairmentChargesRecoveriesAndOtherSpecialCharges"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_RestructuringSettlementAndImpairmentProvisions_c2fb85bc-493a-41c5-9b20-196b63d2faf3" xlink:to="loc_lly_AssetImpairmentChargesRecoveriesAndOtherSpecialCharges_cbf58ccb-3ff3-4093-85fd-abf52b2939b0" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.lilly.com/role/FinancialInstrumentsEffectofRiskManagementInstrumentsDetails" xlink:type="simple" xlink:href="lly-20210930.xsd#FinancialInstrumentsEffectofRiskManagementInstrumentsDetails"/>
  <link:calculationLink xlink:role="http://www.lilly.com/role/FinancialInstrumentsEffectofRiskManagementInstrumentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_lly_DerivativeInstrumentsGainLossRecognized_f9585824-0e40-45d6-8978-e18b2024d208" xlink:href="lly-20210930.xsd#lly_DerivativeInstrumentsGainLossRecognized"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainLossOnForeignCurrencyDerivativeInstrumentsNotDesignatedAsHedgingInstruments_51bac3a4-f3b4-4b36-a5f7-d8eb5a991382" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnForeignCurrencyDerivativeInstrumentsNotDesignatedAsHedgingInstruments"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_lly_DerivativeInstrumentsGainLossRecognized_f9585824-0e40-45d6-8978-e18b2024d208" xlink:to="loc_us-gaap_GainLossOnForeignCurrencyDerivativeInstrumentsNotDesignatedAsHedgingInstruments_51bac3a4-f3b4-4b36-a5f7-d8eb5a991382" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossCashFlowHedgeGainLossReclassificationBeforeTax_865f7d0e-c171-4b9e-b48c-7bc868dcca9c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeLossCashFlowHedgeGainLossReclassificationBeforeTax"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_lly_DerivativeInstrumentsGainLossRecognized_f9585824-0e40-45d6-8978-e18b2024d208" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossCashFlowHedgeGainLossReclassificationBeforeTax_865f7d0e-c171-4b9e-b48c-7bc868dcca9c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ChangeInUnrealizedGainLossOnFairValueHedgingInstruments1_df1b0108-141c-4a8d-8dcc-76c7f792a92f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ChangeInUnrealizedGainLossOnFairValueHedgingInstruments1"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_lly_DerivativeInstrumentsGainLossRecognized_f9585824-0e40-45d6-8978-e18b2024d208" xlink:to="loc_us-gaap_ChangeInUnrealizedGainLossOnFairValueHedgingInstruments1_df1b0108-141c-4a8d-8dcc-76c7f792a92f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ChangeInUnrealizedGainLossOnHedgedItemInFairValueHedge1_1233e077-ed65-482e-84bd-a6f10a81ed23" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ChangeInUnrealizedGainLossOnHedgedItemInFairValueHedge1"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_lly_DerivativeInstrumentsGainLossRecognized_f9585824-0e40-45d6-8978-e18b2024d208" xlink:to="loc_us-gaap_ChangeInUnrealizedGainLossOnHedgedItemInFairValueHedge1_1233e077-ed65-482e-84bd-a6f10a81ed23" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.lilly.com/role/FinancialInstrumentsFairValueofFinancialInstrumentsDetails" xlink:type="simple" xlink:href="lly-20210930.xsd#FinancialInstrumentsFairValueofFinancialInstrumentsDetails"/>
  <link:calculationLink xlink:role="http://www.lilly.com/role/FinancialInstrumentsFairValueofFinancialInstrumentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermInvestments_9503b46a-9d2c-463a-80ba-157ea93e4ee2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongTermInvestments"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLongTermInvestments_b1cf7fd5-c631-4e38-abba-a0c2da01cd0e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherLongTermInvestments"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LongTermInvestments_9503b46a-9d2c-463a-80ba-157ea93e4ee2" xlink:to="loc_us-gaap_OtherLongTermInvestments_b1cf7fd5-c631-4e38-abba-a0c2da01cd0e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquitySecuritiesWithoutReadilyDeterminableFairValueAmount_ce3fb16d-ef96-46ec-ba46-990ad2ea0c1e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesWithoutReadilyDeterminableFairValueAmount"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LongTermInvestments_9503b46a-9d2c-463a-80ba-157ea93e4ee2" xlink:to="loc_us-gaap_EquitySecuritiesWithoutReadilyDeterminableFairValueAmount_ce3fb16d-ef96-46ec-ba46-990ad2ea0c1e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent_0a4abce0-abbf-4827-9a05-f340b988aacd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LongTermInvestments_9503b46a-9d2c-463a-80ba-157ea93e4ee2" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent_0a4abce0-abbf-4827-9a05-f340b988aacd" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquitySecuritiesFvNi_669beec5-18ba-4cf0-aae4-6acc0c8ce086" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesFvNi"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LongTermInvestments_9503b46a-9d2c-463a-80ba-157ea93e4ee2" xlink:to="loc_us-gaap_EquitySecuritiesFvNi_669beec5-18ba-4cf0-aae4-6acc0c8ce086" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.lilly.com/role/FinancialInstrumentsContractualMaturitiesDetails" xlink:type="simple" xlink:href="lly-20210930.xsd#FinancialInstrumentsContractualMaturitiesDetails"/>
  <link:calculationLink xlink:role="http://www.lilly.com/role/FinancialInstrumentsContractualMaturitiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_4e6d5070-7a09-4592-8549-1c072da22c4c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearFairValue_0d544c4d-2404-44d7-a95e-f256ec6296e2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearFairValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_4e6d5070-7a09-4592-8549-1c072da22c4c" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearFairValue_0d544c4d-2404-44d7-a95e-f256ec6296e2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughFiveYearsFairValue_957f8f42-39b3-4047-b4d0-d684c205f314" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughFiveYearsFairValue"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_4e6d5070-7a09-4592-8549-1c072da22c4c" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughFiveYearsFairValue_957f8f42-39b3-4047-b4d0-d684c205f314" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAfterFiveThroughTenYearsFairValue_eb7e6e24-d2f0-4f7c-8c9b-5971d1dda072" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAfterFiveThroughTenYearsFairValue"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_4e6d5070-7a09-4592-8549-1c072da22c4c" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAfterFiveThroughTenYearsFairValue_eb7e6e24-d2f0-4f7c-8c9b-5971d1dda072" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAfterTenYearsFairValue_c9c3c304-faf4-46be-85de-1baa9ffa6613" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAfterTenYearsFairValue"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_4e6d5070-7a09-4592-8549-1c072da22c4c" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAfterTenYearsFairValue_c9c3c304-faf4-46be-85de-1baa9ffa6613" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.lilly.com/role/RetirementBenefitsComponentsofNetPeriodicBenefitCostDetails" xlink:type="simple" xlink:href="lly-20210930.xsd#RetirementBenefitsComponentsofNetPeriodicBenefitCostDetails"/>
  <link:calculationLink xlink:role="http://www.lilly.com/role/RetirementBenefitsComponentsofNetPeriodicBenefitCostDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DefinedBenefitPlanNetPeriodicBenefitCost_7261eec1-8745-499f-85db-92d409b10b07" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DefinedBenefitPlanNetPeriodicBenefitCost"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DefinedBenefitPlanServiceCost_38f8389b-1487-47f3-b6ad-2050adc1c0c0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DefinedBenefitPlanServiceCost"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DefinedBenefitPlanNetPeriodicBenefitCost_7261eec1-8745-499f-85db-92d409b10b07" xlink:to="loc_us-gaap_DefinedBenefitPlanServiceCost_38f8389b-1487-47f3-b6ad-2050adc1c0c0" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DefinedBenefitPlanInterestCost_0bfba553-5b9b-4260-babc-f05d27f8acd1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DefinedBenefitPlanInterestCost"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DefinedBenefitPlanNetPeriodicBenefitCost_7261eec1-8745-499f-85db-92d409b10b07" xlink:to="loc_us-gaap_DefinedBenefitPlanInterestCost_0bfba553-5b9b-4260-babc-f05d27f8acd1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DefinedBenefitPlanExpectedReturnOnPlanAssets_1364e86b-0eef-4144-bd5e-92e7791c7fe4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DefinedBenefitPlanExpectedReturnOnPlanAssets"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DefinedBenefitPlanNetPeriodicBenefitCost_7261eec1-8745-499f-85db-92d409b10b07" xlink:to="loc_us-gaap_DefinedBenefitPlanExpectedReturnOnPlanAssets_1364e86b-0eef-4144-bd5e-92e7791c7fe4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DefinedBenefitPlanAmortizationOfPriorServiceCostCredit_8e9c6bd9-1b4d-42fa-85cd-d2ad41c35f5e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DefinedBenefitPlanAmortizationOfPriorServiceCostCredit"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DefinedBenefitPlanNetPeriodicBenefitCost_7261eec1-8745-499f-85db-92d409b10b07" xlink:to="loc_us-gaap_DefinedBenefitPlanAmortizationOfPriorServiceCostCredit_8e9c6bd9-1b4d-42fa-85cd-d2ad41c35f5e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DefinedBenefitPlanActuarialGainLossImmediateRecognitionAsComponentInNetPeriodicBenefitCostCredit_9bbff73c-cf56-4b72-ac2a-01354e0f0f78" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DefinedBenefitPlanActuarialGainLossImmediateRecognitionAsComponentInNetPeriodicBenefitCostCredit"/>
    <link:calculationArc order="5" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DefinedBenefitPlanNetPeriodicBenefitCost_7261eec1-8745-499f-85db-92d409b10b07" xlink:to="loc_us-gaap_DefinedBenefitPlanActuarialGainLossImmediateRecognitionAsComponentInNetPeriodicBenefitCostCredit_9bbff73c-cf56-4b72-ac2a-01354e0f0f78" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.lilly.com/role/OtherComprehensiveIncomeLossAOCIDetails" xlink:type="simple" xlink:href="lly-20210930.xsd#OtherComprehensiveIncomeLossAOCIDetails"/>
  <link:calculationLink xlink:role="http://www.lilly.com/role/OtherComprehensiveIncomeLossAOCIDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTax_92590188-68ba-4d7c-9bee-c4d14d840a32" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTax"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfTax_f3112beb-95e6-42e6-abdc-c379d3cb7138" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTax_92590188-68ba-4d7c-9bee-c4d14d840a32" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfTax_f3112beb-95e6-42e6-abdc-c379d3cb7138" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTax_e18fc64d-cfe3-4533-a66d-b0fb3134dd0c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTax"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTax_92590188-68ba-4d7c-9bee-c4d14d840a32" xlink:to="loc_us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTax_e18fc64d-cfe3-4533-a66d-b0fb3134dd0c" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.lilly.com/role/OtherNetIncomeExpenseDetails" xlink:type="simple" xlink:href="lly-20210930.xsd#OtherNetIncomeExpenseDetails"/>
  <link:calculationLink xlink:role="http://www.lilly.com/role/OtherNetIncomeExpenseDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonoperatingIncomeExpense_414f5215-1eb7-4426-87ef-b367a8d8a335" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NonoperatingIncomeExpense"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpense_90262cdf-3299-4552-ad54-42992da21c9b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherNonoperatingIncomeExpense"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NonoperatingIncomeExpense_414f5215-1eb7-4426-87ef-b367a8d8a335" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpense_90262cdf-3299-4552-ad54-42992da21c9b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpense_a889f686-fb2a-42c1-ae87-81346886005a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestExpense"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NonoperatingIncomeExpense_414f5215-1eb7-4426-87ef-b367a8d8a335" xlink:to="loc_us-gaap_InterestExpense_a889f686-fb2a-42c1-ae87-81346886005a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_035cf58e-d575-46aa-b8b1-4bd18df0a2f4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainsLossesOnExtinguishmentOfDebt"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NonoperatingIncomeExpense_414f5215-1eb7-4426-87ef-b367a8d8a335" xlink:to="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_035cf58e-d575-46aa-b8b1-4bd18df0a2f4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquitySecuritiesFvNiGainLoss_adc421e1-b3e2-4e6e-ad22-6130c8b03503" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesFvNiGainLoss"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NonoperatingIncomeExpense_414f5215-1eb7-4426-87ef-b367a8d8a335" xlink:to="loc_us-gaap_EquitySecuritiesFvNiGainLoss_adc421e1-b3e2-4e6e-ad22-6130c8b03503" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentIncomeInterest_fbac0a49-ad4b-4708-9034-683a563c1097" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentIncomeInterest"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NonoperatingIncomeExpense_414f5215-1eb7-4426-87ef-b367a8d8a335" xlink:to="loc_us-gaap_InvestmentIncomeInterest_fbac0a49-ad4b-4708-9034-683a563c1097" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetPeriodicDefinedBenefitsExpenseReversalOfExpenseExcludingServiceCostComponent_bc5efc73-2448-43cb-9898-c26606214037" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetPeriodicDefinedBenefitsExpenseReversalOfExpenseExcludingServiceCostComponent"/>
    <link:calculationArc order="6" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NonoperatingIncomeExpense_414f5215-1eb7-4426-87ef-b367a8d8a335" xlink:to="loc_us-gaap_NetPeriodicDefinedBenefitsExpenseReversalOfExpenseExcludingServiceCostComponent_bc5efc73-2448-43cb-9898-c26606214037" xlink:type="arc"/>
  </link:calculationLink>
</link:linkbase>
