In the Upper Colorado River Basin (UCRB), the principal source of water in the southwestern U.S., demand exceeds supply in most years, and will likely continue to rise. While General Circulation Models (GCMs) project surface temperature warming by 3.5 to 5.6°C for the area, precipitation projections are variable, with no wetter or drier consensus. We assess the impacts of projected 21(st) century climatic changes on subbasins in the UCRB using the Soil and Water Assessment Tool, for all hydrologic components (snowmelt, evapotranspiration, surface runoff, subsurface runoff, and streamflow), and for 16 GCMs under the A2 emission scenario. Over the GCM ensemble, our simulations project median Spring streamflow declines of 36% by the end of the 21(st) century, with increases more likely at higher elevations, and an overall range of -100 to +68%. Additionally, our results indicated Summer streamflow declines with median decreases of 46%, and an overall range of -100 to +22%. Analysis of hydrologic components indicates large spatial and temporal changes throughout the UCRB, with large snowmelt declines and temporal shifts in most hydrologic components. Warmer temperatures increase average annual evapotranspiration by ∼23%, with shifting seasonal soil moisture availability driving these increases in late Winter and early Spring. For the high-elevation water-generating regions, modest precipitation decreases result in an even greater water yield decrease with less available snowmelt. Precipitation increases with modest warming do not translate into the same magnitude of water-yield increases due to slight decreases in snowmelt and increases in evapotranspiration. For these basins, whether modest warming is associated with precipitation decreases or increases, continued rising temperatures may make drier futures. Subsequently, many subbasins are projected to turn from semi-arid to arid conditions by the 2080 s. In conclusion, water availability in the UCRB could significantly decline with adverse consequences for water supplies, agriculture, and ecosystem health.