The densely populated plains of the lower Indus Basin largely depend on water resources originating in the mountains of the transboundary upper Indus Basin. Recent studies have improved our understanding of this upstream–downstream linkage and the impact of climate change. However, water use in the mountainous part of the Indus and its hydropolitical implications have been largely ignored. This study quantifies the comparative impact of upper Indus water usage, through space and time, on downstream water availability under future climate change and socio-economic development. Future water consumption and relative pressure on water resources will vary greatly across seasons and between the various sub-basins of the upper Indus. During the dry season, the share of surface water required within the upper Indus is high and increasing, and in some transboundary sub-basins future water requirements exceed availability during the critical winter months. In turn this drives spatiotemporal hotspots to emerge in the lower Indus where seasonal water availability is reduced by over 25 % compared to natural conditions. This will play an important, but previously unaccounted for, compounding role in the steep decline of per capita seasonal water availability in the lower Indus in the future, alongside downstream population growth. Increasing consumption in the upper Indus may thus locally lead to water scarcity issues, and increasingly be a driver of downstream water stress during the dry season. Our quantified perspective on the evolving upstream–downstream linkages in the transboundary Indus Basin highlights that long-term shared water management here must account for rapid socio-economic change in the upper Indus and anticipate increasing competition between upstream and downstream riparian states.