Lithium concentrations in untreated groundwater from 1464 public-supply wells and 1676 domestic-supply wells distributed across 33 principal aquifers in the United States were evaluated for spatial variations and possible explanatory factors. Concentrations nationwide ranged from <1 to 396 μg/L (median of 8.1) for public supply wells and <1 to 1700 μg/L (median of 6 μg/L) for domestic supply wells. For context, lithium concentrations were compared to a Health Based Screening Level (HBSL, 10 μg/L) and a drinking-water only threshold (60 μg/L). These thresholds were exceeded in 45% and 9% of samples from public-supply wells and in 37% and 6% from domestic-supply wells, respectively. However, exceedances and median concentrations ranged broadly across geographic regions and principal aquifers. Concentrations were highest in arid regions and older groundwater, particularly in unconsolidated clastic aquifers and sandstones, and lowest in carbonate-rock aquifers, consistent with differences in lithium abundance among major lithologies and rock weathering extent. The median concentration for public-supply wells in the unconsolidated clastic High Plains aquifer (central United States) was 24.6 μg/L; 24% of the wells exceeded the drinking-water only threshold and 86% exceeded the HBSL. Other unconsolidated clastic aquifers in the arid West had exceedance rates comparable to the High Plains aquifer, whereas no public supply wells in the Biscayne aquifer (southern Florida) exceeded either threshold, and the highest concentration in that aquifer was 2.6 μg/L. Multiple lines of evidence indicate natural sources for the lithium concentrations; however, anthropogenic sources may be important in the future because of the rapid increase of lithium battery use and subsequent disposal. Geochemical models demonstrate that extensive evaporation, mineral dissolution, cation exchange, and mixing with geothermal waters or brines may account for the observed lithium and associated constituent concentrations, with the latter two processes as major contributing factors.