Nonpoint source (NPS) pollution is tightly linked to land use activities that determine the sources and magnitudes of pollutant loadings to stream water. The pollutant loads may also be alleviated within reservoirs because of the physical interception resulting from changed hydrological regimes and other biochemical processes. It is important but challenging to assess the NPS pollution processes with human effects due to the measurement limitations. The objective of this study is to evaluate the effects of human activities such as land uses and reservoir operation on the hydrological and NPS pollution processes in a highly agricultural area-the Iowa River Basin-using the Soil and Water Assessment Tool (SWAT). The evaluation of model performance at multiple sites reveals that SWAT can consistently simulate the daily streamflow, and monthly/annual sediment and nutrient loads (nitrate nitrogen and mineral phosphorus) in the basin. We also used the calibrated model to estimate the trap efficiencies of sediment (~78%) and nutrients (~30%) in the Coralville Reservoir within the basin. These non-negligible effects emphasize the significance of incorporating the sediment and nutrient removal mechanisms into watershed system studies. The spatial quantification of the critical NPS pollution loads can help identify hot-spot areas that are likely locations for the best management practices.