Hydrological drought is characterized by streamflow, which can be significantly impacted by climate and human activities. Previous studies have investigated the impacts of human activities and those of climate change on hydrological conditions separately. In this study, the relative contributions of water management, including local water extraction and reservoir regulation, and climate change to hydrological drought in the 21st century are analyzed using a coupled high-resolution, integrated water model. Simulations were performed for the U.S. under two Representative Concentration Pathway (RCP) scenarios, with and without water management. Using the standardized runoff index (SRI) to quantify hydrological droughts, our results show that at continental scale, water management intensifies droughts mostly due to local water extraction. However, for areas downstream of reservoirs, flow regulation can reduce drought severity and spatial extent, especially during the irrigation season when reservoir release enhances flow. Focusing only on the irrigation season, reservoir regulation reduces mainly moderate droughts but water extraction increases extreme droughts. Our results further show that the net effects of water management on the severity of future hydrological droughts are comparable to the difference between the high emissions scenario (RCP8.5) and the mitigation scenario (RCP4.5).