Changes in the hydrology of high-altitude catchments may have major consequences for downstream water supply. Based on model projections with a higher spatiotemporal resolution and degree of process complexity than any previous intercontinental comparative study, we show that the impacts of climate change cannot be generalized. These impacts range from a high climatic sensitivity, decreasing runoff, and significant seasonal changes in the Central Andes of Chile to increasing future runoff, limited seasonal shifts, but increases in peak flows in the Nepalese Himalaya.