In 2013 to 2015, 833 public supply wells in 15 Principal aquifers in the U.S. were sampled to identify which aquifers contained high methane concentrations (>1 mg/L) and determine the geologic, hydrologic, and geochemical conditions associated with high concentrations. This study represents the first national assessment of methane in aquifers used for public supply in the U.S. and, as such, advances the understanding of the occurrence and distribution of methane in groundwater nationally. Methane concentrations >1 and > 10 mg/L occurred in 6.7 and 1.1% of the samples, respectively. Most high concentrations occurred in aquifers in the Atlantic and Gulf Coastal Plain regions and upper Midwest. High methane concentrations were most commonly associated with Tertiary and younger aquifer sediments, old groundwater (>60 years), and concentrations of oxygen, nitrate-N, and sulfate <0.5 mg/L. Concentrations of methane were also positively correlated (p < 0.05) with dissolved organic carbon and ammonium. Case studies in Florida, Texas, and Iowa were used to explore how regional context from this data set could aid our understanding of local occurrences of methane in groundwater. Regional data for methane, Br/Cl ratios, sulfate, and other parameters helped identify mixing processes involving end members such as wastewater effluent-impacted groundwater, saline formation water, and pore water in glacial till that contributed methane to groundwater in some cases and supported methane oxidation in others.