Millions of people in the geopolitically important region of Central Asia depend on water from snow- and glacier-melt driven international rivers, most of all the Syr Darya and Amu Darya. The riparian countries of these rivers have experienced recurring water allocation conflicts ever since the Soviet Union collapsed. Will climate change exacerbate water stress and thus conflicts? We have developed a coupled climate, land-ice and rainfall-runoff model for the Syr Darya to quantify impacts and show that climatic changes are likely to have consequences on runoff seasonality due to earlier snow-melt. This will increase water stress in unregulated catchments because less water will be available for irrigation in the summer months. Threats from geohazards, above all glacier lake outbursts, are likely to increase as well. The area at highest risk is the densely populated, agriculturally productive, and politically unstable Fergana Valley. Targeted infrastructural developments will be required in the region. If the current mismanagement of water and energy resources can be replaced with more effective resource allocation mechanisms through the strengthening of transboundary institutions, Central Asia will be able to successfully address these future climate-related challenges.