In order to simulate the potential effect of forecasted land‐cover change on streamflow and water availability, there has to be confidence that the hydrologic model used is sensitive to small changes in land cover (<10%) and that this land‐cover change exceeds the inherent uncertainty in forecasted conditions. To investigate this, a 26‐year streamflow record was simulated for 33 basins (54–928 km2) in the Delaware River Basin using three dates of land cover: the 2011 National Land‐Cover Dataset (Homer, Fry, & Barnes, 2012), 2030 land‐cover conditions representing median values from 101 equally‐likely forecasts, and 2060 land‐cover conditions corresponding to the same iterations used to represent 2030. Streamflow was simulated using a process‐based hydrologic model that includes both pervious and impervious methods as parameterized by three land‐cover‐based hydrologic response units (HRUs)—forested, agricultural, and developed land. Small, but significant differences in streamflow magnitude, variability, and seasonality were seen among the three time periods—2011, 2030, and 2060. Temporal differences were discernible from the range of conditions simulated with 101 equally likely forecasts for 2030. Development was co‐located with the most frequent landscape components, as characterized by topographic wetness index, resulting in a change in hydrology for each HRU, highlighting that knowing the location of disturbance is key to understanding potential streamflow changes. These results show that streamflow simulation using regional calibration that incorporates land‐cover‐based HRUs can be sensitive to relatively small changes in land‐cover and that temporal trends resulting from land‐cover change can be isolated in order to evaluate other changes that might affect water resources.