Abstract This study investigates changes in the hydrologic regime of the Chitral River, Hindukush–Karakoram–Himalayan (HKH) region, Pakistan. Different statistically based methods were used to assess climate change-induced hydrologic alterations that can possibly impact aquatic habitat in the study region. The hydrological model Hydrologiska Byråns Vattenbalansavdelning (HBV) was calibrated, validated, and applied to predict streamflow in the Chitral River basin. The HBV model was forced with the ensemble of four general circulation models under different representative concentration pathway emission scenarios to generate future streamflow under climate change conditions in the basin for the mid-twenty-first century. The results of this study show that hydrologic regimes in the study area, expressed by the magnitude, duration, frequency, timing, and rate of streamflow, are likely to alter in the future. Positive (i.e., with increased frequency) hydrologic alteration is projected for most flow parameters under all scenarios for the 2021–2050 period compared with values observed during the historical period (1976–2005). These hydrologic alterations might have impacts on fish and migratory bird species in the study area. This research can be helpful in providing practical information for more effective water resources and aquatic ecosystem management in the HKH region.