We evaluate the impact of climate change on stream flow in the Upper Mississippi River Basin (UMRB) by using a regional climate model (RCM) coupled with a hydrologic model, the Soil and Water Assessment Tool (SWAT). The SWAT model was calibrated and validated against measured stream flow data using observed weather data and inputs from the Environmental Protection Agency’s BASINS (Better Assessment Science Integrating Point and Nonpoint Sources) geographical information/database system. The combined performance of the SWAT and RCM was examined using observed weather data as a lateral boundary condition in the RCM. The SWAT and RCM were found to perform well, especially on an annual basis. The potential impacts of climate change on water yield and other hydrologic budget components were then quantified by driving SWAT with current and future climates. A 21 percent increase in future precipitation simulated by the RCM produced an 18 percent increase in snowfall, a 51 percent increase in surface runoff, and a 43 percent increase in groundwater recharge, resulting in a 50 percent net increase in total water yield in the UMRB on an annual basis. Uncertainty analysis showed that the simulated change in stream flow substantially exceeded model biases of the combined modeling system (with the largest bias being 18 percent), giving us relatively high confidence in the results.