Water availability on the continents is important for human health, economic activity, ecosystem function and geophysical processes. Because the saturation vapour pressure of water in air is highly sensitive to temperature, perturbations in the global water cycle are expected to accompany climate warming. Regional patterns of warming-induced changes in surface hydroclimate are complex and less certain than those in temperature, however, with both regional increases and decreases expected in precipitation and runoff. Here we show that an ensemble of 12 climate models exhibits qualitative and statistically significant skill in simulating observed regional patterns of twentieth-century multidecadal changes in streamflow. These models project 10–40% increases in runoff in eastern equatorial Africa, the La Plata basin and high-latitude North America and Eurasia, and 10–30% decreases in runoff in southern Africa, southern Europe, the Middle East and mid-latitude western North America by the year 2050. Such changes in sustainable water availability would have considerable regional-scale consequences for economies as well as ecosystems.