We examine major reorganizations of the terrestrial ecosystem around Mono Lake, California during the last deglacial period from 16,000–9,000 cal yr BP using pollen, microcharcoal, and coprophilous fungal spores (Sporormiella) from a deep-water sediment core. The pollen results record the assemblage, decline, and replacement of a mixed wooded community of Sierran and Great Basin taxa with Alkali Sink and Sagebrush Steppe biomes around Mono Lake. In particular, the enigmatic presence of Sequoiadendron-type pollen and its extirpation during the early Holocene hint at substantial biogeographic reorganizations on the Sierran-Great Basin ecotone during deglaciation. Rapid regional hydroclimate changes produced structural alterations in pine–juniper woodlands facilitated by increases in wildfires at 14,800 cal yr BP, 13,900 cal yr BP, and 12,800 cal yr BP. The rapid canopy changes altered the availability of herbaceous understory plants, likely putting pressure on megafauna populations, which declined in a stepwise fashion at 15,000 cal yr BP and 12,700 cal yr BP before final extirpation from Mono Basin at 11,500 cal yr BP. However, wooded vegetation communities overall remained resistant to abrupt hydroclimate changes during the late Pleistocene; instead, they gradually declined and were replaced by Alkali Sink communities in the lowlands as temperature increased into the Early Holocene, and Mono Lake regressed.