During the late Pleistocene, emergent groundwater supported persistent and long-lived desert wetlands in many broad valleys and basins in the American Southwest. When active, these systems provided important food and water sources for local fauna, supported hydrophilic and phreatophytic vegetation, and acted as catchments for eolian and alluvial sediments. Desert wetlands are represented in the geologic record by groundwater discharge deposits, which are also called spring or wetland deposits. Groundwater discharge deposits contain information on the timing and magnitude of past changes in water-table levels and, thus, are a source of paleohydrologic and paleoclimatic information. Here, we present the results of an investigation of extensive groundwater discharge deposits in the central Mojave Desert at Valley Wells, California. We used geologic mapping and stratigraphic relations to identify two distinct wetland sequences at Valley Wells, which we dated using radiocarbon, luminescence, and uranium-series techniques. We also analyzed the sediments and microfauna (ostracodes and gastropods) to reconstruct the specific environments in which they formed. Our results suggest that the earliest episode of high water-table conditions at Valley Wells began ca. 60 ka (thousands of calendar yr B.P.), and culminated in peak discharge between ca. 40 and 35 ka. During this time, cold (4–12 °C) emergent groundwater supported extensive wetlands that likely were composed of a wet, sedge-rush-tussock meadow mixed with mesic riparian forest. After ca. 35 ka, the water table dropped below the ground surface but was still shallow enough to support dense stands of phreatophytes through the Last Glacial Maximum (LGM). The water table dropped further after the LGM, and xeric conditions prevailed until modest wetlands returned briefly during the Younger Dryas cold event (13.0–11.6 ka). We did not observe any evidence of wet conditions during the Holocene at Valley Wells. The timing of these fluctuations is consistent with changes in other paleowetland systems in the Mojave Desert, the nearby Great Basin Desert, and in southeastern Arizona, near the border of the Sonoran and Chihuahuan Deserts. The similarities in hydrologic conditions between these disparate locations suggest that changes in groundwater levels during the late Pleistocene in desert wetlands scattered throughout the American Southwest were likely driven by synoptic-scale climate processes.