The U.S. Geological Survey’s (USGS) SPAtially Referenced Regression On Watershed attributes (SPARROW) model was used to aid in the interpretation of monitoring data and simulate streamflow and water-quality conditions in streams across the Midwest Region of the United States. SPARROW is a hybrid empirical/process-based mass balance model that can be used to estimate the major sources and environmental factors that affect the long-term supply, transport, and fate of contaminants in streams. The spatially explicit model structure is defined by a river reach network coupled with contributing catchments. The model is calibrated by statistically relating watershed sources and transport-related properties to monitoring-based water-quality load estimates. This USGS data release includes input and output files associated with 2012 SPARROW simulations of streamflow, total nitrogen, total phosphorus and suspended-sediment load in streams of the Midwest. Model construction, calibration and results are described in Robertson and Saad (2019, https://doi.org/10.3133/sir20195114).