The drainage system in south-central Africa has undergone major reorganisations since the disruption of Gondwana. Isopachs of the Kalahari sequence and a variety of geomorphological features can be used to pinpoint abandoned drainage lines. Continental fluvial sediments of Mesozoic-Cenozoic age reflect river systems which existed prior to and immediately following continental break-up. The east coast sedimentary sequence documents changes in the location of major supplies of terrigenous sediments, and provides a framework for establishing the timing of changes in drainage configuration. This evidence indicates that during the upper Jurassic to Cretaceous, the Okavango, Cuando and Zambezi-Luangwa rivers formed the headwaters of the proto-Limpopo. The lower-Zambezi-Shire formed a separate graben-bound river system with a discharge point into the Indian Ocean in the vicinity of mouth of the present-day Zambezi. A third major drainage entered the Indian in the vicinity of the modern Save mouth. End Cretaceous uplift along the Okavango-Kalahari-Zimbabwe Axis severed the links between the Limpopo and the Okavango, Cuando and Zambezi-Luangwa. This resulted in a senile endoreic drainage system which supplied sediment to the Kalahari basin. However, the uplift rejuvenated the lower Zambezi, initiating headward erosion and progressive capture of the Luangwa, upper Zambezi and Kafue. Predatory headward extension of the Zambezi is still active, and this river will eventually capture the Okavango. The model developed for drainage reorganisation provides a framework for interpreting kimberlitic heavy mineral dispersion patterns. It also forms the basis for explaining fish and plant dispersion patterns, and understanding recent water level fluctuations in the Makgadigadi pans system in Botswana.