As one of the components comprising food-energy-water systems (FEWS), the energy sector, especially electricity production, is intimately connected to water. Climate extremes-related impacts on water resources will directly affect the interdependence of water, food, and energy. A better understanding of the extent of climate impacts on energy sector and the options to improve water-energy security are needed for planning an overall resilient FEWS. Therefore, we are motivated to examine the climate stress on the thermoelectric power supply using the Water Balance Model coupled with Thermoelectric Power & Thermal Pollution Model (WBM-TP2M), which can simulate water-energy linkages at the power plant, river reach, and regional scales. Using the Midwest (MW) and Northeast (NE) regions as our study area, we design a group of single- and multi-factor experiments both for historical climate period (1980–2019) and a case where we create a series of intensified extremes (2010–2019). The results show that power generation over the two regions features a gradually increasing trend in the past four decades, while, in contrast, thermal pollution has been decreasing steadily since 2005. Heat waves created temporary dips in the generation of electricity and peaks of heavily thermal-polluted stream length. The experiments reveal the significant role of cooling towers in reducing thermal pollution without losing much capacity to generate power, one important measure of resilience against climate extremes. Constraints placed on effluent temperature from the Clean Water Act lead to interrupted operations, which reduces (up to 20%) power generation, increases sensitivity to climatic extremes, but only show a small reduction in thermal pollution. Coal, as a fuel source, is subject to low thermal efficiency and high-water demand, which results in clearly decreased power generation. Overall, our findings suggest that replacing a less thermal-efficient fuel mix and environmentally destructive once-through cooling can move the energy sector towards several beneficial outcomes. Chief among these is a more efficient power production system that uses less water and does so while fostering clean, less carbon-intense technologies (e.g., combined gas cycle turbines, cooling towers, renewable energy), thus linking positive outcomes that simultaneously and positively impact aquatic ecosystems, regional airsheds and human health.