We assess the ability of global water systems, resolved at 282 large river basins or Assessment Sub Regions (ASRs), to the meet water requirements over the coming decades under integrated projections of socioeconomic growth and climate change. We employ a Water Resource System (WRS) component embedded within the MIT Integrated Global System Model (IGSM) framework in a suite of simulations that consider a range of climate policies and regional hydroclimatic changes through the middle of this century. We find that for many developing nations water-demand increases due to population growth and economic activity have a much stronger effect on water stress than climate change. By 2050, economic growth and population change alone can lead to an additional 1.8 billion people living in regions with at least moderate water stress. Of this additional 1.8 billion people, 80% are found in developing countries. Uncertain regional climate change can play a secondary role to either exacerbate or dampen the increase in water stress due to socioeconomic growth. The strongest climate impacts on relative changes in water stress are seen over many areas in Africa, but strong impacts also occur over Europe, Southeast Asia and North America. The combined effects of socioeconomic growth and uncertain climate change lead to a 1.0 to 1.3 billion increase of the world's 2050 projected population living in regions with overly exploited water conditions— where total potential water requirements will consistently exceed surface-water supply. Under the context of the WRS model framework, this would imply that adaptive measures would be taken to meet these surface-water shortfalls and would include: water-use efficiency, reduced and/or redirected consumption, recurrent periods of water emergencies or curtailments, groundwater depletion, additional inter-basin transfers, and overdraw from flow intended to maintain environmental requirements.