Pleistocene climate variability is often seen as a major cause of much of the evidence observed in the archaeological and palaeontological record of Africa. While continent-wide climate systems play an important role when testing pan-African human evolutionary processes, a more focused perspective centred on specific ecosystems at a regional level allows a detailed assessment of the different spatiotemporal scales of the proxies used to reconstruct past environments and the ways humans adapted to their change over time. Recent research in the arid interior of South Africa has provided insights into the availability of freshwater in the open landscape, which is a fundamental factor for human survival and the spatiotemporal distribution of which may have had a major influence on adaptive strategies. This article reviews the Pleistocene archaeological and environmental evidence of the Free State province of South Africa, which has produced major localities such as Cornelia-Uitzoek, Florisbad and Rose Cottage Cave, with the aim of providing a starting point for the discussion over freshwater availability with regard to southern Africa’s Grassland Biome. Particular emphasis is given to the description of multi-proxy approaches including the analysis of sediments, faunal remains, enamel stable isotopes, pollens and phytoliths and absolute dating based on trapped-charge methods. The picture that emerges highlights the paucity of Pleistocene datasets in the Free State and the necessity to expand research at open-air sites and improve the chronological resolution of human occupations and palaeoenvironmental proxies.