Understanding the evolution of river systems in southern Africa is fundamental to constrain the evolution of landscape and sediment dispersal patterns. It is widely considered that the upper Zambezi River was connected with the Limpopo River during the Cretaceous, forming what was then the largest river in Africa. Crustal flexure during the Paleogene severed the upper Zambezi drainage from the Limpopo, setting the framework of the modern Zambezi and Limpopo River systems. We present first evidence—based on heavy-mineral assemblages from cores drilled offshore of the Limpopo River mouth and samples collected in different reaches of the modern Limpopo River, integrated with magnetic susceptibility, detrital-zircon geochronology, and geomorphological analysis—suggesting that the current Limpopo River formed recently in the Plio-Quaternary. Plio-Quaternary climate change is envisaged to have controlled the recent dynamics of river drainage and consequent distribution of sediment loads, as observed in many other transcontinental rivers worldwide