Mountain areas provide disproportionally high runoff in many parts of the world, but their importance for water resources and food production has not been clarified from the viewpoint of the lowland areas downstream. Here we quantify the extent to which lowland inhabitants potentially depend on runoff contributions from mountain areas (39% of the global land mass). We show that ~1.5 billion people (24% of the world’s lowland population) are projected to depend critically on runoff contributions from mountains by the mid-twenty-first century under a ‘middle of the road’ scenario, compared with ~0.2 billion (7%) in the 1960s. This striking rise is mainly due to increased local water consumption in the lowlands, whereas changes in mountain and lowland runoff play only a minor role. We further show that one-third of the global lowland area equipped for irrigation is currently located in regions that both depend heavily on runoff contributions from mountains and make unsustainable use of local blue water resources, a figure that is likely to rise to well over 50% in the coming decades. Our findings imply that mountain areas should receive particular attention in water resources management and underscore the protection they deserve in efforts towards sustainable development.