Based on genetic studies, a Pleistocene Kalahari “palaeo-wetland”, which spanned the region of the Okavango Delta and the Makgadikgadi Basin, was recently considered the geographic origin of evolutionary modern humans. It was proposed that subsequent out-of-homeland migration was induced by climate shifts. The Tsodilo Hills, which are in relative proximity to the Okavango Delta, represent a site of ancient human occupation since at least 100 ka. Local hydrological dynamics were predominately controlled by climate variability and are archived in the sediments of Palaeolake Tsodilo. This study seeks to better understand the Late Pleistocene environments of the ancient Tsodilo people with a focus on palaeo-hydrological settings, which played a major role for their livelihoods.Our multidisciplinary approach included different remote sensing and geophysical methods, comprehensive application of differential GPS, and sedimentological analyses concentrating on the lake beds. Four palaeo-shorelines could be identified, three of which indicate highstands during which the Tamacha palaeo-river drained Palaeolake Tsodilo towards the Okavango Panhandle. Two highstands during MIS 3b and LGM are related to periods of largely increased fish consumption by humans as has been documented by archaeologists. The palaeolake was likely most extended about 100 ka ago or earlier, when it covered ca. 70 km2 and was 16 m deep. A single (neo-)tectonic fault could be detected.We assume that the Tamacha palaeo-river was a gateway for ancient humans to reach the Tsodilo Hills from these palaeo-wetlands. The people took advantage of the Tsodilo Hills as shelter from weather hazards and as a natural fortress against predators and elephants. Geologically, the Tsodilo Hills were comparatively calm. They represented a relatively safe haven where the social behaviour of early modern humans could evolve to a higher complexity, which relates to the fundamental question when and where modern human behaviour began.