Thermoelectric power plants with once-through cooling systems generated 30% (∼300 GW) of U.S. electricity in 2016. Factors that reduce once-through cooling capacity and thus power output are environmental regulations, warming surface waters, and drought. The latter two may become more frequent as global climate changes. Previous research indicates that reduction in power plant capacity caused by environmental regulations can be significant while that by surface water warming is minor. Here, we address the effect of droughts on power output, which until now has remained conflated with temperature impacts. We do this using a widely used electricity generation model alongside hourly operational and meteorological data for 52 once-through plants located across the U.S. The effect of drought on plant output is examined for different water-availability and temperature scenarios, with and without regulations on plant water discharge. We find that if surface waters warm 3 °C and river discharges drop 20%, droughts would account for ≤20% of total capacity reduction depending on the plant, warming surface waters ≤2.3%, and environmental regulations up to 80%. This suggests that maintaining environmental regulations will require the continued conversion of plant cooling systems from once-through to recirculating, and mitigating climate impacts will require more stringent drought-specific watershed management.