The main freshwater source of arid/semi-arid Central Asia is stored in its high mountain glaciers. Water for the downstream countries is mainly supplied through the Syrdarya River that originates at the confluence of the Naryn and Karadarya rivers in the Ferghana Valley. Runoff generation from glaciers plays a crucial role, although a considerable number of small tributaries supply the river with additional runoff from snowmelt and rain in the mountains surrounding the Ferghana Valley. Observations of rising air temperature and accelerated glacier shrinkage make it most likely that the relative contributions of the smaller tributaries will increase. Hitherto, assessments of climate change effects on the water resource availability have largely neglected the growing importance of the runoff from smaller tributaries. We used a dynamically downscaled A1B SRES scenario for climate change effects for the period 2071–2100 in relation to the reference period of 1971–2000 and a version of the conceptual hydrological Hydrologiska Byråns Vattenavdelning model (HBV-light) to estimate runoff contributions with particular respect to the small tributaries. The simulations showed a 12–42% decrease in summer runoff; and a 44–107% increase in winter-spring runoff. This indicates the hydrological regime is shifting towards a runoff from snowmelt earlier in the year. The study suggests that actions for climate change adaptation should be complemented by land management configured to secure optimal runoff supplement from the smaller catchments.