Climatic and hydrological changes will likely be intensified in the Upper Blue Nile (UBN) basin by the effects of global warming. The extent of such effects for representative concentration pathways (RCP) climate scenarios is unknown. We evaluated projected changes in rainfall and evapotranspiration and related impacts on water availability in the UBN under the RCP4.5 scenario. We used dynamically downscaled outputs from six global circulation models (GCMs) with unprecedented spatial resolution for the UBN. Systematic errors of these outputs were corrected and followed by runoff modelling by the HBV (Hydrologiska ByrånsVattenbalansavdelning) model, which was successfully validated for 17 catchments. Results show that the UBN annual rainfall amount will change by −2.8 to 2.7% with a likely increase in annual potential evapotranspiration (in 2041–2070) for the RCP4.5 scenario. These changes are season dependent and will result in a likely decline in streamflow and an increase in soil moisture deficit in the basin.