Glaciers and seasonal snow of the Upper Indus Basin (UIB) play a critical role in sustaining river flow and water security across South Asia. However, ongoing climate warming is expected to substantially alter snowmelt and glacier-fed hydrological regimes. This study evaluates the sensitivity of runoff generation to future climate change using the Snowmelt Runoff Model (SRM) driven by CMIP6 climate projections under SSP2-4.5 and SSP5-8.5 scenarios. The model was calibrated and validated using observed discharge, temperature, and snow-cover data from glacierized catchments of the UIB, demonstrating satisfactory performance with Nash–Sutcliffe Efficiency (NSE) values of 0.78–0.86 and coefficient of determination (R²) values exceeding 0.80. Climate projections indicate significant warming throughout the twenty-first century, with mean annual temperatures projected to increase by 2.3–2.8 °C under SSP2-4.5 and 4.8–5.9 °C under SSP5-8.5 relative to the 1981–2010 baseline. Simulations suggest enhanced snow and ice melt during the mid-century period, leading to increased runoff and an earlier occurrence of peak discharge. Peak flows are projected to occur approximately 2–4 weeks earlier than present conditions, reflecting shifts in the timing of meltwater generation. Under continued warming, seasonal runoff patterns are expected to become increasingly variable, with greater discharge during spring and early summer and reduced water availability during late summer. These projected changes highlight the sensitivity of glacier-fed river systems to climatic forcing and underscore the importance of incorporating cryospheric change into long-term water-resource planning and adaptation strategies across High Mountain Asia.