The U.S. Geological Survey collected groundwater samples from 67 wells and 1 spring used for domestic and small system drinking water supplies in Placer, El Dorado, Amador, and Calaveras Counties, California in 2016-2017. The sites were sampled for the Mokelumne, Cosumnes, and American River Watersheds (MCAW) Shallow Aquifer Study Unit of the California State Water Resources Control Board Groundwater Ambient Monitoring and Assessment (GAMA) Program Priority Basin Project’s assessment of the quality of groundwater resources used for domestic and small system drinking water supplies. Domestic and small-system wells commonly are screened at shallower depths than public-supply wells. The MCAW study unit covered the parts of the Upper Mokelumne, Upper Cosumnes, and South and North Fork American River watersheds [8-digit hydrologic unit codes (HUC8) 18040012, 18040013, 18020129, and 18020128] in the Sierra Nevada hydrogeologic province. Wells in the MCAW study unit generally tap hard-rock aquifer systems composed of volcanic, granitic, or metamorphic rocks. The study unit was divided into equal area grid cells and one well or spring was sampled in each cell. Groundwater samples were analyzed for field water-quality parameters, volatile organic compounds, pesticides and pesticide degradates, nutrients, major ions and trace elements, hexavalent chromium, perchlorate, gross alpha and gross beta particle activities, tritium, carbon-14 in dissolved inorganic carbon, stable isotopic ratios of water and dissolved nitrate, and microbial indicators. These data support the following publication: Fram, M.S., and Shelton, J.L., 2018, Groundwater Quality in the Mokelumne, Cosumnes, and American River Watersheds, Sierra Nevada, California: U.S. Geological Survey Open-File Report 2018-1047, 4p., https://doi.org/10.3133/ofr20181047.