Maintaining water availability and electric energy production are the major concerns for the future in countries which are extremely dependent on their water resources like Brazil. The objective of this study was to assess the impacts of climate change on streamflow and therefore on hydropower potential of the Grande river basin headwater region, Southeast Brazil. For this purpose, the SWAT model was used to simulate the hydrological behaviour of the headwaters under the Representative Concentration Pathways 4.5 and 8.5 scenarios, obtained from the Regional Climate Models Eta‐HadGEM‐ES and Eta‐MIROC5 between the years 2007 and 2099. Through power duration curves we estimated the hypothetical average annual energy production at three hydropower plants installed in cascade in the region, being, from upstream to downstream, Camargos, Itutinga and Funil. These plants account for a potential of 277 MW. SWAT was able to simulate the streamflow of the Grande river basin headwaters and, therefore, to reproduce the observed monthly streamflow from the baseline period (1961–2005) reasonably well for all three hydropower plants. In general, the results indicated a significant streamflow reduction and therefore reductions in runoff during all the simulated periods and all radiative forcing analysed, when compared to the baseline period. Thus, these results led to reductions in hydropower potential and hence decreases of the annual energy production varying from 6.1 to 58.6% throughout the 21st Century.