Abstract The Greater Horn of Africa region increasingly experiences high risk of water scarcity. A combination of frequent droughts, rapid population growth and rising urbanisation has reduced streamflow and intensified water abstraction, causing water and food shortages. Estimates of future streamflow changes in the region have so far been highly uncertain and evaluations using ground-based measurements are still limited. Here, future streamflow changes are estimated using a distributed hydrological model forced with an ensemble of high-resolution climate simulations produced using the European community Earth-System Model v3.1. The simulated streamflow is evaluated using observed data from 29 stations from river basins across different climate zones in the region. Evaluation results show large sub-regional variations in the performance of simulated streamflow. The sign and magnitude of future streamflow changes vary between climate simulations and river basins, highlighting the uncertainties in the hydrologic projections. Overall, the streamflow projections indicate large (seasonal, long-term mean and extreme) streamflow decreases for all major rivers in Ethiopia and increases in the equatorial parts of the region at the end of the century. The ensemble mean shows a 10 to 25% decrease in the long-term mean flow in Ethiopia and a 10% increase in the equatorial part of the region in 2080s. Similarly, there is a substantial change in high flows in 2080s, with up to -,50% reduction in the northern and 50% increase in the equatorial parts of the region. These findings are critical because the rivers provide water supply to a rapidly changing socio-economy of the region.