Water scarcity conditions over the 21st century both globally and regionally are assessed in the context of climate change and climate mitigation policies, by estimating both water availability and water demand within the Global Change Assessment Model (GCAM), a leading community-integrated assessment model of energy, agriculture, climate, and water. To quantify changes in future water availability, a new gridded water-balance global hydrologic model – namely, the Global Water Availability Model (GWAM) – is developed and evaluated. Global water demands for six major demand sectors (irrigation, livestock, domestic, electricity generation, primary energy production, and manufacturing) are modeled in GCAM at the regional scale (14 geopolitical regions, 151 sub-regions) and then spatially downscaled to 0.5° × 0.5° resolution to match the scale of GWAM. Using a baseline scenario (i.e., no climate change mitigation policy) with radiative forcing reaching 8.8 W m−2 (equivalent to the SRES A1Fi emission scenario) and three climate policy scenarios with increasing mitigation stringency of 7.7, 5.5, and 4.2 W m−2 (equivalent to the SRES A2, B2, and B1 emission scenarios, respectively), we investigate the effects of emission mitigation policies on water scarcity. Two carbon tax regimes (a universal carbon tax (UCT) which includes land use change emissions, and a fossil fuel and industrial emissions carbon tax (FFICT) which excludes land use change emissions) are analyzed. The baseline scenario results in more than half of the world population living under extreme water scarcity by the end of the 21st century. Additionally, in years 2050 and 2095, 36% (28%) and 44% (39%) of the global population, respectively, is projected to live in grid cells (in basins) that will experience greater water demands than the amount of available water in a year (i.e., the water scarcity index (WSI) > 1.0). When comparing the climate policy scenarios to the baseline scenario while maintaining the same baseline socioeconomic assumptions, water scarcity declines under a UCT mitigation policy but increases with a FFICT mitigation scenario by the year 2095, particularly with more stringent climate mitigation targets. Under the FFICT scenario, water scarcity is projected to increase, driven by higher water demands for bio-energy crops.