MHC region showed strongest rapid evolution in Stone Age Europe. MHC had excess Mesolithic hunter-gatherer ancestry despite overall 20% HG in late Stone Age genomes. Late Neolithic MHC ancestry was 50:50 HG-farmer instead of mostly farmer. Selection preserved local European HG immune variants during farming transition. HG likely carried adaptations to Europe-specific diseases or pathogens. MHC diversity from HG aided resistance to farming-linked infections. Neolithic farmers from Near East brought skin pigmentation genes preferentially selected for vitamin D. Farming lifestyle intensified selection on immunity genes due to animal proximity and diet. No excess farmer ancestry expected in MHC given disease pressures. HG immune genes transmitted preferentially to descendants. Greater MHC diversity matched or exceeded adaptation benefits. Confirmed prior findings on Near Eastern pigmentation introgression. Ancient DNA from 677 Stone Age Europeans analyzed. Neolithic transition drove immune evolution worldwide. Local HG genetics buffered farmer disease vulnerabilities. MHC evolution predates or parallels farming arrival.