We present a hydroclimate synthesis of the southern Great Basin over the last two glacial-interglacial cycles focused on paleolakes in Death Valley (core DV93-1), Searles Valley (core SLAPP-SRLS17), Owens Valley (core OL92), and the Devils Hole cave. There is close agreement between the occurrence of lakes in Death Valley and the height of the water table in the Devils Hole (50 km east of Death Valley) during the last 200 kyr. Death Valley and Devils Hole have adjacent, partly overlapping, drainage areas and most likely did over the last 200 kyr. When the water table in the Devils Hole was above the threshold level of ∼5 m higher than the modern, permanent lakes existed in Death Valley. At water table elevations less than 5 m above the modern, ephemeral lakes, saline pans, and mudflats occurred in Death Valley. The close temporal agreement between inferred paleoenvironments from the sediments in the Death Valley core and the paleowater table elevation in Devils Hole suggests a common forcing and provides insight into climate variability in the southwestern United States over the last 200 kyr. Owens Valley and Searles Valley, which derived inflow waters from the Sierra Nevada via the Owens River, contain paleohydrologic records which match those from Death Valley and the Devils Hole in terms of timing and direction of water availability over the last 200 kyr, indicating a similar paleohydrologic history for the entire southern Great Basin region. Near the end of Marine Oxygen Isotope Stage 6 (MIS 6), 140 ka - 130 ka, Lake Manly in Death Valley became shallow and hypersaline, and ultimately dried up at 127.1 ka ±4.3 ka. The transition from glacial to interglacial vegetation, which involved the loss of Juniperus pollen and an increase in Quercus (oak) pollen, occurred in Death Valley core DV93-1 at 131.3 ka ±4.0 ka. Following the glacial to interglacial pollen shift, a large alkaline lake formed in Death Valley. Similar conditions (freshwater, high productivity, and a mixed, deeply oxygenated water column indicated by biomarkers) existed in Searles Lake between 135.3 ^+2.7/_-2.9 ka and 130.1^+2.7/_-2.6 ka, also following the juniper-oak pollen transition. Sr isotopes in calcite and sulfate minerals (gypsum, glauberite, thenardite), and the rare occurrence of the sodium carbonate mineral northupite with a low ⁸⁷Sr/⁸⁶Sr ratio in core DV93-1, together with organic geochemical proxies from Searles core SLAPP-SRLS17, all suggest that at this time, late MIS 6 Lake Manly in Death Valley received alkaline water via spillover from Searles Valley into Death Valley through Panamint Valley. The hydrologic connection between Searles Valley, Panamint Valley, and Death Valley at Termination II (130 ka) is documented here for this system of pluvial lakes for the first time. The Devils Hole water table decreased to +6.5 m at 140.8 ka ±3.2 ka, rose briefly to +8 m at 137.6 ka ±0.5 ka, and then dropped 8 m by 120.36 ka ±0.45 ka, when it reached an elevation similar to the modern. The pluvial lakes in Death Valley and Searles Valley may have coincided with the rise of the Devils Hole water table at ∼137.6 ka ±0.5 ka years ago, although the age models for core DV93-1 and core SLAPP-SLRS17 during the end of MIS 6 carry large uncertainties.