Watershed modeling in 20 large, United States (U.S.) watersheds addresses gaps in our knowledge of streamflow, nutrient (nitrogen and phosphorus), and sediment loading sensitivity to mid-21st Century climate change and urban/residential development scenarios. Use of a consistent methodology facilitates regional scale comparisons across the study watersheds. Simulations use the Soil and Water Assessment Tool. Climate change scenarios are from the North American Regional Climate Change Assessment Program dynamically downscaled climate model output. Urban and residential development scenarios are from U.S. Environmental Protection Agency's Integrated Climate and Land Use Scenarios project. Simulations provide a plausible set of streamflow and water quality responses to mid-21st Century climate change across the U.S. Simulated changes show a general pattern of decreasing streamflow volume in the central Rockies and Southwest, and increases on the East Coast and Northern Plains. Changes in pollutant loads follow a similar pattern but with increased variability. Ensemble mean results suggest that by the mid-21st Century, statistically significant changes in streamflow and total suspended solids loads (relative to baseline conditions) are possible in roughly 30-40% of study watersheds. These proportions increase to around 60% for total phosphorus and total nitrogen loads. Projected urban/residential development, and watershed responses to development, are small at the large spatial scale of modeling in this study.