A geographic information system (GIS)-based water-budget framework has been developed to study the climate-change impact on regional groundwater recharge, and it was applied to the Southern Hills aquifer system of southwestern Mississippi and southeastern Louisiana, USA. The framework links historical climate variables and future emission scenarios of climate models to a hydrologic model, HELP3, to quantify spatiotemporal potential recharge variations from 1950 to 2099. The framework includes parallel programming to divide a large amount of HELP3 simulations among multiple cores of a supercomputer, to expedite computation. The results show that a wide range of projected potential recharge for the Southern Hills aquifer system resulted from the divergent projections of precipitation, temperature and solar radiation using three scenarios (B1, A2 and A1FI) of the National Center for Atmospheric Research’s Parallel Climate Model 1 (PCM) and the National Oceanic and Atmospheric Administration Geophysical Fluid Dynamics Lab’s (GFDL) model. The PCM model projects recharge change ranging from −33.7 to +19.1 % for the 21st century. The GFDL model projects less recharge than the PCM, with recharge change ranging from −58.1 to +7.1 %. Potential recharge is likely to increase in 2010–2039, but likely to decrease in 2070–2099. Projected recharge is more sensitive to the changes in the projected precipitation than the projected solar radiation and temperature. Uncertainty analysis confirms that the uncertainty in projected precipitation yields more changes in the potential recharge than in the projected temperature for the study area.