Lithium concentrations in untreated groundwater from 1,464 public-supply wells, 1,676 domestic-supply wells, and 1,560 monitoring wells distributed across 33 principal aquifers in the United States were evaluated for spatial variations and possible explanatory factors. For context, lithium concentrations are compared to a drinking-water only threshold (60 mg/L) and a Health-Based Screening Level (HBSL, 10 mg/L). These thresholds were exceeded in 9 percent and 45 percent of samples from public-supply wells and in 6 percent and 37 percent from domestic-supply wells, respectively. Exceedances were most frequent for arid regions and older groundwater. Groundwater lithium concentrations were highest in unconsolidated clastic aquifers and sandstones and lowest in carbonate-rock aquifers, consistent with differences in lithium abundance among lithologies. Groundwater from unconsolidated clastic aquifers of the western region exhibited the highest concentrations owing to the small volume of recharge, extensive evaporation, mineral dissolution, cation exchange, and mixing with geothermal waters or brines. Geochemical models indicate cation exchange and mixing with saline groundwaters as major contributing factors. Of the public-supply wells in the unconsolidated clastic High Plains aquifer, 24 percent exceeded the drinking-water only threshold and 86 percent exceeded the HBSL. Other unconsolidated clastic aquifers in the arid west had comparable exceedances. Multiple lines of evidence indicate natural sources for the lithium concentrations.