This USGS data release contains long-term mean annual total nitrogen and total phosphorus load estimates, and the model coefficients used to obtain the load estimates, for streams in the Midwest Region of the United States. The loads were estimated using the Fluxmaster program (Schwarz and others, 2006, https://pubs.usgs.gov/tm/2006/tm6b3) with a 5-parameter model and detrending to 2012 following the methods described in Saad and others, 2011 (https://doi.org/10.1111/j.1752-1688.2011.00575.x). A subset of these load estimates are described in Robertson and Saad, 2021 (https://doi.org/10.1111/1752-1688.12905) and were used to evaluate differences in load estimates in the Mississippi/Atchafalaya River Basin based on this method and the methods described in Saad and others, 2019 (https://dx.doi.org/10.3133/sir20195069). The flow and water-quality input files necessary to reproduce the load estimates included in this data release can be found in Saad and others, 2019 (https://doi.org/10.5066/F7DN436B).