This study is based on both the recent and the predicted twenty first century climatic and hydrological changes over the mountainous Upper Indus Basin (UIB), which are influenced by snow and glacier melting. Conformal-Cubic Atmospheric Model (CCAM) data for the periods 1976–2005, 2006–2035, 2041–2070, and 2071–2100 with RCP4.5 and RCP8.5; and Regional Climate Model (RegCM) data for the periods of 2041–2050 and 2071–2080 with RCP8.5 are used for climatic projection and, after bias correction, the same data are used as an input to the University of British Columbia (UBC) hydrological model for river flow projections. The projections of all of the future periods were compared with the results of 1976–2005 and with each other. Projections of future changes show a consistent increase in air temperature and precipitation. However, temperature and precipitation increase is relatively slow during 2071–2100 in contrast with 2041–2070. Northern parts are more likely to experience an increase in precipitation and temperature in comparison to the southern parts. A higher increase in temperature is projected during spring and winter over southern parts and during summer over northern parts. Moreover, the increase in minimum temperature is larger in both scenarios for all future periods. Future river flow is projected by both models to increase in the twenty first century (CCAM and RegCM) in both scenarios. However, the rate of increase is larger during the first half while it is relatively small in the second half of the twenty first century in RCP4.5. The possible reason for high river flow during the first half of the twenty first century is the large increase in temperature, which may cause faster melting of snow, while in the last half of the century there is a decreasing trend in river flow, precipitation, and temperature (2071–2100) in comparison to 2041–2070 for RCP4.5. Generally, for all future periods, the percentage of increased river flow is larger in winter than in summer, while quantitatively large river flow was projected, particularly during the summer monsoon. Due to high river flow and increase in precipitation in UIB, water availability is likely to be increased in the twenty first century and this may sustain water demands.