A large international watershed, the St. Clair‐Detroit River System, containing both extensive urban and agricultural areas, was modeled using the Soil and Water Assessment Tool (SWAT) model. The watershed, located in southeastern Michigan, United States, and southwestern Ontario, Canada, encompasses the St. Clair, Clinton, Detroit (DT), Sydenham (SY), Upper, and Lower Thames subwatersheds. The SWAT input data and model resolution (i.e., hydrologic response units, HRUs), were established to mimic farm boundaries, the first time this has been done for a watershed of this size. The model was calibrated (2007–2015) and validated (2001–2006) with a mix of manual and automatic methods at six locations for flow and water quality at various time scales. The model was evaluated using Nash–Sutcliffe efficiency and percent bias and was used to explore major water quality issues. We showed the importance of allowing key parameters to vary among subwatersheds to improve goodness of fit, and the resulting parameters were consistent with subwatershed characteristics. Agricultural sources in the Thames and SY subwatersheds and point sources from DT subwatershed were major contributors of phosphorus. Spatial distribution of phosphorus yields at HRU and subbasin levels identified locations for potential management targeting for both point and nonpoint sources and revealed that in some subwatersheds nonpoint sources are dominated by urban sources.