The Soil and Water Assessment Tool (SWAT) uses hydrologic response units (HRUs) as the basic unit of all model calculations. ArcSWAT, the ArcGIS interface for SWAT, allows users to specify thresholds of land cover, soil, and slope in defining HRUs to improve the computational efficiency of simulations while keeping key landscape features of a watershed in the hydrologic modeling. However, this study found that applying commonly used thresholds in defining HRUs may lead to considerable loss of information about the watershed landscape, emphasizing larger soil types on smaller land covers once the land covers meet a threshold for land cover, and potentially changing average slopes. These changes often have a minor effect on water yield and streamflow simulations by SWAT but a larger effect on sediment and nutrient load simulations, which are more sensitive to slope and soil type and are more influential on outputs at the subwatershed than at the watershed outlet. Study results can help modelers improve their understanding of the HRU strategy for simplifying watershed representation while maintaining major landscape features and make decisions in the HRU delineation process to minimize the chance of biased simulations.