Central Asia is positioned at a crossroads linking several zones important to hominin dispersal during the Middle Pleistocene. However, the scarcity of stratified and dated archaeological material and paleoclimate records makes it difficult to understand dispersal and occupation dynamics during this time period, especially in arid zones. Here we compile and analyze paleoclimatic and archaeological data from Pleistocene Central Asia, including examination of a new layer-counted speleothem-based multiproxy record of hydrological changes in southern Uzbekistan at the end of MIS 11. Our findings indicate that Lower Palaeolithic sites in the steppe, semi-arid, and desert zones of Central Asia may have served as key areas for the dispersal of hominins into Eurasia during the Middle Pleistocene. In agreement with previous studies, we find that bifaces occur across these zones at higher latitudes and in lower altitudes relative to the other Paleolithic assemblages. We argue that arid Central Asia would have been intermittently habitable during the Middle Pleistocene when long warm interglacial phases coincided with periods when the Caspian Sea was experiencing consistently high water levels, resulting in greater moisture availability and more temperate conditions in otherwise arid regions. During periodic intervals in the Middle Pleistocene, the local environment of arid Central Asia was likely a favorable habitat for paleolithic hominins and was frequented by Lower Paleolithic toolmakers producing bifaces.