The onset and intensification of eolian activity mark climatic transitions that promote wide-scale aridification, recorded by the generation and preservation of massive sand deposits. Evaluating the impact and implications of such repositories on Earth systems requires knowledge about the timing of their emplacement and the mechanisms responsible for their generation, which remain highly uncertain. Here we provide time constraints for the establishment of the Kalahari Erg, which is the largest continuous body of sand on Earth. We apply cosmogenic nuclide dating of sand from the Kalahari Desert combined with numerical modeling to determine when sand was introduced into the interior of southern Africa. Through the consideration of several scenarios, we show that major events of eolian sand transport and accumulation occurred between ~2.5 and 1 Myr ago. This substantial activity, which significantly altered environmental settings, corresponds to regional, continental, and global scale morphotectonic and climatic changes that contributed to the mass production and widespread dispersion of sand. These changes substantially altered existing habitats, thus constituting a crucial milestone for hominin evolution and migration throughout the African continent during the Pleistocene.