The U.S. Geological Survey collected groundwater samples from 46 wells used for domestic and small system drinking water supplies in San Joaquin, Calaveras, and Stanislaus counties, California in 2019. The wells were sampled for the Northern San Joaquin Valley Domestic-Supply 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 are commonly screened at shallower depths than public-supply wells. The Northern San Joaquin Valley study unit encompasses the Eastern San Joaquin groundwater subbasin of the San Joaquin Valley groundwater basin. The study unit was divided into 50 equal area grid cells and a domestic or small-system well was sampled in 46 of those cells. Groundwater samples from the 46 wells were analyzed for field water-quality parameters, volatile organic compounds, pesticides and pesticide degradates, nutrients, major ions and trace elements, hexavalent chromium, perchlorate, per- and polyfluoroalkyl substances (PFAS), tritium, carbon-14 in dissolved inorganic carbon, stable isotopes of water and nitrate, and microbial indicators. This data release supports the following publication: Levy, Z.F., Balkan, M., and Shelton, J.L., 2021, Quality of groundwater used for domestic supply in the northern San Joaquin Valley, California: U.S. Geological Survey Fact Sheet 2021-3040, 4 p., https://doi.org/10.3133/fs20213040.