Groundwater supplies 50% of drinking water worldwide, but compromised water quality from anthropogenic and geogenic contaminants can limit usage of groundwater as a drinking water source. Groundwater quality in the glacial aquifer system, USA (GLAC), is presented in the context of a hydrogeologic framework that divides the study area into 17 hydrogeologic terranes. Results are reported at aquifer-system scale and regional (terrane) scale. This paper presents a quantitative assessment of groundwater quality in the GLAC using data from numerous sources for samples collected 2005–2013, compared to health-based and aesthetic (non-health) benchmarks, and evaluated with areal and population metrics. Concentrations above a benchmark are considered high. Trace elements are widespread across the study area, with an estimated 5.7 million people relying on groundwater with high concentrations of one or more trace elements; manganese and arsenic are most often at high concentration. Nitrate is found at high concentration in 4.0% of the study area, serving about 740 thousand people. Organic compounds including pesticides and volatile organic compounds are high in 2.0% of the assessed study area, with about 870 thousand people relying on groundwater with high concentrations of an organic compound. High arsenic and manganese concentrations occur primarily in the terranes with thick, stratigraphically complex, fine-grained glacial sediment, coincident with groundwater under reducing conditions (indicated by iron concentrations >100 μg/L); high nitrate is uncommon in those same terranes. When nitrate is high in thick, fine-grained, complex terranes, though, it is much more commonly associated with groundwater under more oxidizing conditions. Common geogenic trace elements occur at high concentration due to characteristic geologic and geochemical conditions. Conversely, anthropogenic nitrate and organic compounds are introduced at or near the land surface. High concentrations of nitrate or organic compounds are generally limited to areas in proximity where people live and use the chemicals.