The transition to agriculture was a transformative process in human history with wide-ranging demographic and social consequences1. Across South America, agriculture was adopted at different times and through diverse pathways, resulting in a mosaic of regionally distinct farming histories2,3. The Uspallata Valley, at the southern frontier of Andean farming, offers a unique opportunity to examine a case of late adoption of agriculture. Here we show that agriculture in the Uspallata Valley was adopted by local hunter-gatherers, as evidenced by genetic continuity between pre-farming and farming populations inferred from 46 newly sequenced ancient human genomes. These groups carried a distinct genetic component in Indigenous American diversity, indicating a unique population history in the region. Palaeodietary isotopes (δ13C/δ15N) reveal fluctuating maize intake consistent with flexible farming. Strontium isotopes (87Sr/86Sr) indicate the arrival of migrants from nearby regions between around 810–700 cal years BP, shortly before the Inka expansion. Genomic and isotopic analyses show that these migrants belonged to the same regional metapopulation as local groups, relied heavily on maize, probably moved in matrilineally organized family groups, exhibited stress markers (including malnutrition and diseases, such as tuberculosis, as confirmed by pathogen genomics) and experienced a long-term demographic decline. Our results suggest that these groups used social organization and migration as resilience strategies in the face of a multidimensional crisis.
