The Grand Canyon in northern Arizona is an international tourist destination, a home or sacred place to many Native Americans, and hosts some of the highest-grade uranium deposits in the United States. Although potential contamination of water resources by uranium from mining activities is a concern, other elements commonly associated with these uranium deposits may pose a greater risk to human populations in the area. This study presents an assessment of arsenic in groundwater in the Grand Canyon area. First, sampling results for arsenic are presented and areas with elevated arsenic concentrations are discussed. Potential pathways of groundwater contamination by arsenic from uranium mines are then discussed to elucidate situations and conditions under which elevated concentrations of arsenic might be expected to become mobilized from breccia-pipe uranium mining activities. Results for arsenic in groundwater in the study area were available for 652 samples collected from 230 sites. Arsenic concentrations in groundwater ranged from less than reporting limits in 60 samples to a maximum concentration of 875 μg/L at Pumpkin Spring. About 88% (202) of the sites sampled had a maximum arsenic concentration below the drinking water standard of 10 μg/L. Available data from near former or current breccia-pipe uranium mines in the area indicate limited evidence to-date of mining effects on elevated arsenic in groundwater, although slow groundwater flow paths in the region may result in extended times of decades or more for groundwater to reach discharge locations. Post-mining entry of groundwater into the shaft and underground mine workings, with subsequent transport of metal-enriched groundwater offsite, may be a potential pathway of groundwater arsenic contamination from mining, although concentrations would likely be attenuated by contact with sedimentary rock units and dilution with native groundwater along flow paths. Monitoring of perched groundwater at reclaimed mine sites post-reclamation could provide data on the effectiveness of clean-closure practices on protecting groundwater quality in the area.