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

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2026 Workiva-->
<!--r:01a044bc-60df-7716-ab92-200799c4d22c,g:2f0afd51-c116-4c49-b501-5997dce0f36a-->
<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" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
  <link:roleRef roleURI="http://mckesson123.com/role/CoverPage" xlink:type="simple" xlink:href="mck-20260825.xsd#CoverPage"/>
  <link:definitionLink xlink:role="http://mckesson123.com/role/CoverPage" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityInformationLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntitiesTable_01a044bc-60df-721e-8dfb-4b9b15148e99" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntitiesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_EntitiesTable_01a044bc-60df-721e-8dfb-4b9b15148e99" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_01a044bc-60df-7904-bca2-d8abe7223386" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_dei_EntitiesTable_01a044bc-60df-721e-8dfb-4b9b15148e99" xlink:to="loc_us-gaap_StatementClassOfStockAxis_01a044bc-60df-7904-bca2-d8abe7223386" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_01a044bc-60df-7904-bca2-d8abe7223386_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_01a044bc-60df-7904-bca2-d8abe7223386" xlink:to="loc_us-gaap_ClassOfStockDomain_01a044bc-60df-7904-bca2-d8abe7223386_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_01a044bc-60df-728f-904e-430921e3b5c8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_01a044bc-60df-7904-bca2-d8abe7223386" xlink:to="loc_us-gaap_ClassOfStockDomain_01a044bc-60df-728f-904e-430921e3b5c8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_01a044bc-60df-75cf-9f31-36ba68f74cfc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_01a044bc-60df-728f-904e-430921e3b5c8" xlink:to="loc_us-gaap_CommonStockMember_01a044bc-60df-75cf-9f31-36ba68f74cfc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mck_A0.625notesDue2021Member_01a044bc-60df-7401-ae65-b3e553c0eb67" xlink:href="mck-20260825.xsd#mck_A0.625notesDue2021Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_01a044bc-60df-728f-904e-430921e3b5c8" xlink:to="loc_mck_A0.625notesDue2021Member_01a044bc-60df-7401-ae65-b3e553c0eb67" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mck_A1.500NotesDue2025Member_01a044bc-60df-73d9-8e6b-16cf886ecc7b" xlink:href="mck-20260825.xsd#mck_A1.500NotesDue2025Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_01a044bc-60df-728f-904e-430921e3b5c8" xlink:to="loc_mck_A1.500NotesDue2025Member_01a044bc-60df-73d9-8e6b-16cf886ecc7b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mck_A1.625NotesDue2026Member_01a044bc-60df-717d-b0ce-0aa4da697006" xlink:href="mck-20260825.xsd#mck_A1.625NotesDue2026Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_01a044bc-60df-728f-904e-430921e3b5c8" xlink:to="loc_mck_A1.625NotesDue2026Member_01a044bc-60df-717d-b0ce-0aa4da697006" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mck_A3.125NotesDue2029Member_01a044bc-60df-7fb4-96da-13f70867a4c6" xlink:href="mck-20260825.xsd#mck_A3.125NotesDue2029Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_01a044bc-60df-728f-904e-430921e3b5c8" xlink:to="loc_mck_A3.125NotesDue2029Member_01a044bc-60df-7fb4-96da-13f70867a4c6" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentType_01a044bc-60df-716c-a579-2e06fefa23bd" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_DocumentType"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_DocumentType_01a044bc-60df-716c-a579-2e06fefa23bd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentPeriodEndDate_01a044bc-60df-7eb7-adf2-7e3dc2f8075c" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_DocumentPeriodEndDate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_DocumentPeriodEndDate_01a044bc-60df-7eb7-adf2-7e3dc2f8075c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityRegistrantName_01a044bc-60df-7a13-a8c6-9b6484b8cae7" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityRegistrantName"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_EntityRegistrantName_01a044bc-60df-7a13-a8c6-9b6484b8cae7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityCentralIndexKey_01a044bc-60df-70ce-889a-28b41b67bf12" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityCentralIndexKey"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_EntityCentralIndexKey_01a044bc-60df-70ce-889a-28b41b67bf12" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityFileNumber_01a044bc-60df-7536-8492-863f82d148ac" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityFileNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_EntityFileNumber_01a044bc-60df-7536-8492-863f82d148ac" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityIncorporationStateCountryCode_01a044bc-60df-7a9d-bf87-cb9bd88c7fe1" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityIncorporationStateCountryCode"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_EntityIncorporationStateCountryCode_01a044bc-60df-7a9d-bf87-cb9bd88c7fe1" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityTaxIdentificationNumber_01a044bc-60df-7f05-a128-97bbef436809" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityTaxIdentificationNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_EntityTaxIdentificationNumber_01a044bc-60df-7f05-a128-97bbef436809" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressAddressLine1_01a044bc-60df-72c3-9e18-adec3c499343" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityAddressAddressLine1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_EntityAddressAddressLine1_01a044bc-60df-72c3-9e18-adec3c499343" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressCityOrTown_01a044bc-60df-747e-9428-980696cf9e05" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityAddressCityOrTown"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_EntityAddressCityOrTown_01a044bc-60df-747e-9428-980696cf9e05" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressStateOrProvince_01a044bc-60df-78ee-8661-1559c2b6a273" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityAddressStateOrProvince"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_EntityAddressStateOrProvince_01a044bc-60df-78ee-8661-1559c2b6a273" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressPostalZipCode_01a044bc-60df-7df1-b58c-f3bb219c8e49" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityAddressPostalZipCode"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_EntityAddressPostalZipCode_01a044bc-60df-7df1-b58c-f3bb219c8e49" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_SecurityExchangeName_01a044bc-60df-7e73-b040-e74a86b07ee6" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_SecurityExchangeName"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_SecurityExchangeName_01a044bc-60df-7e73-b040-e74a86b07ee6" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_CityAreaCode_01a044bc-60df-7588-9063-709c78259517" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_CityAreaCode"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_CityAreaCode_01a044bc-60df-7588-9063-709c78259517" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_LocalPhoneNumber_01a044bc-60df-7ca0-82c5-11109878c6db" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_LocalPhoneNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_LocalPhoneNumber_01a044bc-60df-7ca0-82c5-11109878c6db" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_Security12bTitle_01a044bc-60df-7865-9ee6-88dcbc7fee2f" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_Security12bTitle"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_Security12bTitle_01a044bc-60df-7865-9ee6-88dcbc7fee2f" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_TradingSymbol_01a044bc-60df-7d04-afd7-8e18b0179aaf" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_TradingSymbol"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_TradingSymbol_01a044bc-60df-7d04-afd7-8e18b0179aaf" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_WrittenCommunications_01a044bc-60df-79ec-b12b-9ffd2e11449b" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_WrittenCommunications"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_WrittenCommunications_01a044bc-60df-79ec-b12b-9ffd2e11449b" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_SolicitingMaterial_01a044bc-60df-754e-866a-495b908c354a" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_SolicitingMaterial"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_SolicitingMaterial_01a044bc-60df-754e-866a-495b908c354a" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_PreCommencementIssuerTenderOffer_01a044bc-60df-7e2f-aebb-850a47c4a7c7" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_PreCommencementIssuerTenderOffer"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_PreCommencementIssuerTenderOffer_01a044bc-60df-7e2f-aebb-850a47c4a7c7" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_PreCommencementTenderOffer_01a044bc-60df-7908-b841-7bf005953ccb" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_PreCommencementTenderOffer"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_PreCommencementTenderOffer_01a044bc-60df-7908-b841-7bf005953ccb" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityEmergingGrowthCompany_01a044bc-60df-7927-84b8-22726eb43612" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityEmergingGrowthCompany"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_EntityEmergingGrowthCompany_01a044bc-60df-7927-84b8-22726eb43612" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_AmendmentFlag_01a044bc-60df-7d51-a528-ff39e1355c7e" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_AmendmentFlag"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityInformationLineItems_01a044bc-60df-77e1-821a-47cd4b23f790" xlink:to="loc_dei_AmendmentFlag_01a044bc-60df-7d51-a528-ff39e1355c7e" xlink:type="arc" order="21"/>
  </link:definitionLink>
</link:linkbase>
