Desert wetlands are keystone ecosystems in arid environments and are preserved in the geologic record as groundwater discharge (GWD) deposits. GWD deposits are inherently discontinuous and stratigraphically complex, which has limited our understanding of how desert wetlands responded to past episodes of rapid climate change. Previous studies have shown that wetlands responded to climate change on glacial to interglacial timescales, but their sensitivity to short-lived climate perturbations is largely unknown. Here, we show that GWD deposits in the Las Vegas Valley (southern Nevada, United States) provide a detailed and nearly complete record of dynamic hydrologic changes during the past 35 ka (thousands of calibrated 14C years before present), including cycles of wetland expansion and contraction that correlate tightly with climatic oscillations recorded in the Greenland ice cores. Cessation of discharge associated with rapid warming events resulted in the collapse of entire wetland systems in the Las Vegas Valley at multiple times during the late Quaternary. On average, drought-like conditions, as recorded by widespread erosion and the formation of desert soils, lasted for a few centuries. This record illustrates the vulnerability of desert wetland flora and fauna to abrupt climate change. It also shows that GWD deposits can be used to reconstruct paleohydrologic conditions at millennial to submillennial timescales and informs conservation efforts aimed at protecting these fragile ecosystems in the face of anthropogenic warming.