The aim of this study was to investigate the impacts of future climate change on discharge and evapotranspiration of the Upper Blue Nile (UBN) basin using multiple global circulation models (GCMs) projections and multiple hydrological models (HMs). The uncertainties of projections originating from HMs, GCMs, and representative concentration pathways (RCPs) were also analyzed. This study is part of the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP) initiative (phase 2), which is a community driven modeling effort to assess global socio-economic impacts of climate change. The baseline period of 1981–2010 was used to identify climate change signals in two future periods: mid future (2036–2065) and far future (2070–2099). Our analyses showed that two out of four GCMs indicated a statistically significant increase in projected precipitation in the far future period. The projected change in mean annual precipitation varied between 4 and 10% relative to the baseline period. The HMs did not agree on the direction of climate change impacts on mean annual discharge. Furthermore, simulated changes in mean annual discharge by all HMs, except SWIM which simulated up to 6.6% increase for the far future period, were not statistically significant. All the HMs generally simulated a statistically significant increase in annual mean actual evapotranspiration (AET) in both periods. The HMs simulated changes in AET ranging from 1.9 to 4.4% for the far future period. In the UBN basin GCM structure was the main contributor of uncertainty in mean annual discharge projection followed by HM structure and RCPs, respectively. The results from this research suggest to use multiple impact models as well as multiple GCMs to provide a more robust assessment of climate change impacts in the UBN basin.