Water withdrawal for electricity generation in the United States accounts for approximately half the total freshwater withdrawal. With steadily growing electricity demands, a changing climate, and limited water supplies in many water-scarce states, meeting future energy and water demands poses a significant socioeconomic challenge. Employing an integrated modeling approach that captures the energy–water interactions at regional and national scales can improve our understanding of the key drivers that govern those interactions and the role of national policies. In this study, the Global Change Assessment Model (GCAM), a technologically-detailed integrated model of the economy, energy, agriculture and land use, water, and climate systems, was extended to model the electricity and water systems at the state level in the U.S. (GCAM-USA). GCAM-USA was employed to estimate future state-level electricity generation and consumption, and their associated water withdrawals and consumption under a set of seven scenarios with extensive detail on the generation fuel portfolio, cooling technology mix, and their associated water use intensities. These seven scenarios were explored to investigate the implications of socioeconomic development and growing electricity demands, cooling system transitions, adoption of water-saving technologies, climate mitigation policy and electricity trading options on future water demands of the U.S. electric-sector. Our findings include: 1) decreasing water withdrawals and increasing water consumption from the conversion from open-loop to closed-loop cooling systems; 2) different energy-sector water demand behaviors with alternative pathways to the mitigation goal; 3) open trading of electricity benefiting energy-scarce yet demand-intensive states; 4) across-state homogeneity under certain driving forces (e.g., climate mitigation and water-saving technologies) and mixed effects under other drivers (e.g.,, electricity trade); and 5) a clear trade-off between water consumption and withdrawal for the electricity sector in the U.S. The paper discusses this withdrawal–consumption trade-off in the context of current national policies and regulations that favor decreasing withdrawals (and increasing consumptive use), and the role of water-saving technologies. The study also clearly shows that climate mitigation strategies focusing on CCS and nuclear power will have less favorable water consumption effects than strategies that support renewable energy and water-saving technologies. The highly-resolved nature of this study, both geographically and technologically, provides a useful platform to address scientific and policy relevant and emerging issues at the heart of the water–energy nexus in the U.S.