Streamflow in high-mountain Asia is influenced by meltwater from snow and glaciers, and determining impacts of climate change on the region’s cryosphere is essential to understand future water supply. Past and future changes in seasonal snow are of particular interest, as specifics at the scale of the full region are largely unknown. Here we combine models with observations to show that regional snowmelt is a more important contributor to streamflow than glacier melt, that snowmelt magnitude and timing changed considerably during 1979–2019 and that future snow meltwater supply may decrease drastically. The expected changes are strongly dependent on the degree of climate change, however, and large variations exist among river basins. The projected response of snowmelt to climate change indicates that to sustain the important seasonal buffering role of the snowpacks in high-mountain Asia, it is imperative to limit future climate change.