The Late Holocene Dry Period (LHDP) was a one-plus millennial megadrought (3100–1800 cal BP) that delivered challenges and windfalls to Indigenous communities of the central Great Basin (United States). New pollen and sedimentation rate studies, combined with existing tree-ring data, submerged stump ages, and lake-level evidence, demonstrate that the LHDP was the driest Great Basin climate within the last 6,000 years—more extreme than the well-known Medieval Climatic Anomaly. New evidence reported here documents that most Great Basin archaeological sites south of 40° N latitude were abandoned during the long dry phase of the LHDP (3100–2200 cal BP), sometimes reoccupied during a wet interval (2200–2000 cal BP), and abandoned again during the most extreme drought (2000–1800 cal BP). Even in the face of epic drought, this is a story of remarkable survivance by some people who adjusted to their drought-stricken landscape where they had lived for millennia. Some moved on, but other resilient foragers refused to abandon their homeland, taking advantage of glacier-fed mountain springs with cooler alpine temperatures and greater moisture retention at high altitude, a result of early Neoglaciation conditions across many Great Basin ranges, despite epic drought conditions in the lowlands.