Better characterization of the geochemical evolution of groundwater south of Grand Canyon, Arizona (USA), is needed to understand natural conditions and assess potential effects from breccia-pipe uranium mining in the region. Geochemical signatures of groundwater at 28 sampling locations were evaluated; baseline concentrations for select trace elements (As, B, Ba, Cr, Li, Mo, Rb, Se, Sr, Th, Tl, U, V) were established, and anomalous chemistry characteristics were identified. Concentrations at some groundwater sites exceeded the USEPA drinking water standard for As of 10 μg/L (Red Canyon, Miners, JT, Havasu, and Warm Springs) and U of 30 μg/L (Salt Creek Spring). Four springs from the study area (Blue, Havasu, Fern, and Warm Springs) had unique chemistry, which may indicate a deep flow path or potential contribution of fluids from lower in the crust. Other springs in the study area were distinguished by major anion water type: sulfate, bicarbonate, and a mixture of the two. Water type distinctions were somewhat spatially segregated, with sulfate type present on the western side of the study area, bicarbonate type on the eastern side, and a mixture of the two interspersed between the endmember sites. Sulfate-type water from this study area had low strontium isotopic ratio (87Sr/86Sr) values. The location of spring discharge within single drainages of the Grand Canyon may influence chemistry, as groundwater discharging from bedrock was altered after flowing through alluvial material. Geochemical analysis of groundwater in Grand Canyon indicates the importance of continued monitoring and better understanding of short-term chemical fluctuations.