Considering that past climate changes have significantly impacted groundwater resources, quantitative predictions of climate change effects on groundwater recharge may be valuable for effective management of future water resources. This study used 16 global climate models (GCMs) and three global warming scenarios to investigate changes in groundwater recharge rates for a 2050 climate relative to a 1990 climate in the U.S. High Plains region. Groundwater recharge was modeled using the Soil-Vegetation-Atmosphere-Transfer model WAVES for a variety of soil and vegetation types representative of the High Plains. The median projection under a 2050 climate includes increased recharge in the Northern High Plains (+8%), a slight decrease in the Central High Plains (−3%), and a larger decrease in the Southern High Plains (−10%), amplifying the current spatial trend in recharge from north to south. There is considerable uncertainty in both the magnitude and direction of these changes in recharge projections. Predicted changes in recharge between dry and wet future climate scenarios encompass both an increase and decrease in recharge rates, with the magnitude of this range greater than 50% of current recharge. On a proportional basis, sensitivity of recharge to changes in rainfall indicates that areas with high current recharge rates are least sensitive to change in rainfall and vice versa. Sensitivity analyses indicate an amplification of change in recharge compared to change in rainfall, and this amplification is in the range of 1–6 with an average of 2.5–3.5 depending upon the global warming scenario.