The U.S. Environmental Protection Agency characterized sediments and seeps/springs in the San Juan watershed located in southwestern Colorado and the four corners region of Colorado, New Mexico, Arizona, and Utah (western United States). The Datasets contain field and laboratory data that resulted from that sampling. Samples for this project were collected from 2018 to 2021. Results of new Pb isotope ratio measurements are provided for sediments (n = 96) collected from across the watershed and seeps/springs (n = 73) from the mineralized headwaters region of the watershed. The Microsoft Excel spreadsheets contain sample data and Quality Control data, including results of primary standards, second source standards, and sample duplicate analyses.