Cities are concentrations of socio-political power and prime architects of land transformation, while also serving as consumption hubs of “hard” water and energy infrastructures (e.g. electrical power, stormwater management, zoning, water supply, and wastewater). These infrastructures extend well outside metropolitan boundaries and impact distal river ecosystems. We used a comprehensive model to quantify the roles of anthropogenic stressors on hydrologic alteration and biodiversity in US streams and isolated the impacts stemming from hard infrastructure developments in cities. Across the conterminous US, cities’ hard infrastructures have significantly altered at least 7% of streams, which influence habitats for over 60% of North America’s fish, mussel, and crayfish species. Additionally, city infrastructures have contributed to local extinctions in 260 species and currently influence 970 indigenous species, 27% of which are in jeopardy. We find that ecosystem impacts do not scale with city size but are instead proportionate to infrastructure decisions. For example, Atlanta’s impacts by hard infrastructures extend across four major river basins, 12,500 stream km, and contribute to 100 local extinctions of aquatic species. In contrast, Las Vegas, a similar size city, impacts < 1000 stream km, leading to only 7 local extinctions. So, cities have local policy choices that can reduce future impacts to regional aquatic ecosystems as cities grow. By coordinating policy and communication between hard infrastructure sectors, local city governments and utilities can directly improve environmental quality in a significant fraction of the nation’s streams and aquatic biota reaching far beyond their city boundaries.