The magnitude and frequency of hydrometeorological extremes are expected to increase in the conterminous United States (CONUS) over the rest of this century, and their increase will significantly impact water resource management. While previous efforts focused on the effects of reservoirs on downstream discharge, the effects of climate change on reservoir inflows in upstream areas are not well understood. We evaluated the large-scale climate change effects on extreme hydrological events and their implications for reservoir inflows in 178 headwater basins across CONUS using the Variable Infiltration Capacity (VIC) hydrologic model. The VIC model was forced with a 10-member ensemble of global circulation models under the Representative Concentration Pathway 8.5 that were dynamically downscaled using a regional climate model (RegCM4) and bias-corrected to 1/24° grid cell resolution. The results projected an increase in the likelihood of flood risk by 44% for a majority of subbasins upstream of flood control reservoirs in the central United States and increased drought risk by 11% for subbasins upstream of hydropower reservoirs across the western United States. Increased risk of both floods and droughts can potentially make reservoirs across CONUS more vulnerable to future climate conditions. This study estimates reservoir inflow changes over the next several decades, which can be used to optimize water supply management downstream.