This data release is in support of a comprehensive study to evaluate water-quality trends in the International Souris River Basin, Saskatchewan and Manitoba, Canada and North Dakota, United States. The effort was completed by the U.S. Geological Survey (USGS) in cooperation with the International Joint Commission and International Souris River Board. This data release contains all files necessary to run trend models and produce results published in U.S. Geological Scientific Investigations Report 2023-XXXX [Nustad, R.A., and Tatge, W.S., 2023, Comprehensive Water-Quality Trend Analysis for Selected Sites and Constituents in the International Souris River Basin, Saskatchewan and Manitoba, Canada and North Dakota, United States, 1970-2020: U.S. Geological Survey Scientific Investigations Report 2023-XXXX]. In addition, this data release contains data for reservoir and Canadian streamflow, and water-quality by group (MI = major ion and dissolved solids, NUT = nutrients, PHY = physical parameters) contained in comma separated values (csv) files (site_flow and country/province_data) for selected sites used in trend and spatial analysis of the Souris River Basin. Streamflow data for the selected United States sites were gathered from the National Water Information System (https://nwis.waterdata.usgs.gov/nwis). Water-quality data for the selected sites in the United States were gathered from the National Water Quality Monitoring Council Water Quality Portal (https://www.waterqualitydata.us/) and collected by two additional agencies; the North Dakota Department of Environmental Quality and the U.S. Geological Survey Dakota Water Science Center. For additional information see metadata file specific to each dataset.