Climate variability and change impact both water demand and water availability for power generation because of the interconnected relationship between water and thermoelectric power generation. To assess the impacts of climate change on water demand by thermoelectric power plants, this study developed a framework that integrates the characteristics of power plants and the results of the Integrated Environmental Control Model (IECM) and the General Circulation Model (GCM) to simulate the water demand. This study contributed a novel tool to assess climate change impacts on water demand based on local climate conditions. This framework was applied to thermoelectric power plants in Illinois to explore the water demand at daily, monthly, and annual temporal resolutions. The results demonstrated that water use is more sensitive at shorter timescales. Thus, it is important to examine the water-energy nexus at a finer temporal resolution. Results also indicated that water consumption is more sensitive to climate change than withdrawal; power plants with a wet cooling tower are more sensitive than ones with a once-through cooling system; and natural gas-fired power plants are more sensitive than coal-fired plants. The case study demonstrated the novel framework is capable to assess climate change impact on water demand of thermoelectric power plants at varying temporal resolutions and the framework is easily applicable to other parts of the world.