Consumptive water use in the Zambezi river basin (ZRB), one of the largest freshwater catchments in Africa and worldwide, is currently around 15-20% of total runoff. This suggests many development possibilities, particularly for irrigated agriculture and hydropower production. Development plans of the riparian countries indicate that consumptive water use might increase up to 40% of total runoff already by 2025. We have constructed a rainfall–runoff model for the ZRB that is calibrated on the best available runoff data for the basin. We then feed a wide range of water demand drivers as well as climate change predictions into the model and assess their implications for runoff at key points in the water catchment. The results show that, in the absence of effective international cooperation on water allocation issues, population and economic growth, expansion of irrigated agriculture, and water transfers, combined with climatic changes are likely to have very important transboundary impacts. In particular, such impacts involve drastically reduced runoff in the dry season and changing shares of ZRB countries in runoff and water demand. These results imply that allocation rules should be set up within the next few years before serious international conflicts over sharing the Zambezi’s waters arise.