Watershed modeling was conducted in 20 large, U.S. watersheds to characterize the sensitivity of streamflow, nutrient (nitrogen and phosphorus), and sediment loading to a range of plausible mid-21st century climate change and urban development scenarios. The study also provides an improved understanding of methodological challenges associated with integrating existing tools (e.g., climate models, downscaling approaches, and watershed models) and data sets to address these scientific questions. The study uses a scenario-analysis approach with a consistent set of watershed models and scenarios applied to multiple locations throughout the nation. Study areas were selected to represent a range of geographic, hydrologic, and climatic characteristics. Watershed simulations were conducted using the Soil Water Assessment Tool (SWAT) and Hydrologic Simulation Program―FORTRAN (HSPF) models. Scenarios of future climate change were developed based on statistically and dynamically downscaled climate model simulations representative of the period 2041−2070. Scenarios of urban and residential development for this same period were developed from the EPA’s Integrated Climate and Land Use Scenarios (ICLUS) project. Future changes in agriculture and human use and management of water were not evaluated.