Urban areas are hot spots that drive multisector environmental change (1, 2). Consumption and production of resources for use within urban environments have local and remote implications for ecosystem services, hydroclimate, energy provision, health, and other factors of human wellbeing (1, 3). In semiarid regions, continued conversion of existing lands to urban landscapes has the potential to drive significant local and regional climate change, compounding global warming (4). At the same time, how cities choose to expand and develop will be critical to defining how successful society will be in adapting to global change. Because cities are, in a real sense, fundamental units of both climate change adaptation and mitigation, development choices in the coming century will lead to either significant exacerbation or significant reduction in the impacts of global change (5). In this study, we explore the sensitivity of regional climate to megapolitan expansion at a nationwide scale across the United States for a range of built environment growth and adaptation scenarios. This work advances the broader dialogue about global climate change, urban resilience, the interface between adaptation and mitigation, tradeoffs among strategies, and sustainability.