The Soil and Water Assessment Tool (SWAT) model was used to assess the effects of potential future climate change on the hydrology of the Upper Mississippi River Basin (UMRB). Calibration and validation of SWAT were performed using monthly stream flows for 1968–1987 and 1988–1997, respectively. The R² and Nash-Sutcliffe simulation efficiency values computed for the monthly comparisons were 0.74 and 0.69 for the calibration period and 0.82 and 0.81 for the validation period. The effects of nine 30-year (1968 to 1997) sensitivity runs and six climate change scenarios were then analyzed, relative to a scenario baseline. A doubling of atmospheric CO₂ to 660 ppmv (while holding other climate variables constant) resulted in a 36 percent increase in average annual streamflow while average annual flow changes of −49, −26, 28, and 58 percent were predicted for precipitation change scenarios of −20, −10, 10, and 20 percent, respectively. Mean annual streamflow changes of 51,10, 2, −6, 38, and 27 percent were predicted by SWAT in response to climate change projections generated from the CISRO-RegCM2, CCC, CCSR, CISRO-Mk2, GFDL, and HadCMS general circulation model scenarios. High seasonal variability was also predicted within individual climate change scenarios and large variability was indicated between scenarios within specific months. Overall, the climate change scenarios reveal a large degree of uncertainty in current climate change forecasts for the region. The results also indicate that the simulated UMRB hydrology is very sensitive to current forecasted future climate changes.