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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. Plain Language Summary: Landscape evolution, sediment dispersal patterns, and the accumulation of hydrocarbon and mineral resources in southern Africa, were largely determined by the evolution of the vast Zambezi‐Limpopo River system. It is widely believed that this river system attained its current configuration during the late Paleogene as a consequence of mantle‐driven dynamic uplift. Based on heavy‐mineral assemblages from river sediments and an International Ocean Discovery Program ocean core, we argue here instead for a Plio‐Pleistocene age for the formation of the modern characteristics of the Limpopo River (i.e., tens of millions of years younger than previously thought). This challenges the current paradigm on both formation modality and driving mechanisms of this vast river system. Plio‐Pleistocene climate change is envisaged to have controlled the dynamics of river drainage and consequent distribution of sediment loads, as observed in several other transcontinental rivers worldwide, underscoring the importance of these climate changes in driving river evolution world‐wide. Key Points: The modern Limpopo River of South Africa formed in the Plio‐PleistocenePlio‐Pleistocene drainage reorganization was driven by climate changeFormation age and driving mechanisms of South African rivers are revisited [ABSTRACT FROM AUTHOR]