Arsenic (As) and uranium (U) contamination in drinking water affects millions of individuals across the US. This issue is particularly acute across rural populations where many people obtain drinking water from unregulated private wells. One specific location greatly affected by high levels of As and U in both surface and groundwater is the Northern Plains of the USA. However, the environmental and anthropogenic factors responsible for the mobilization and heterogeneous distribution of As and U in the waters of this region remain poorly characterized. Groundwater recharge sources and the flow path of water supplying surface water can strongly influence the mobilization and accumulation of aqueous As and U. To understand how hydrologic process affect the distribution of these metals we relied on stable water isotopes (δ2H, δ18O, δ17O). Here we collected stream and spring water samples from 44 locations across South Dakota and Nebraska and measured stable water isotopes (δ2H, δ18O, δ17O) to determine the sources of recharge/inflow to both surface water and groundwater (e.g., heavily evaporated surface water, snow melt, precipitation). We observe strong positive correlations between As and U and stable water isotopes – a finding that suggests that mobilization of these elements is occurring under oxic conditions, mobilization is delocalized, and As and U are likely accumulating along the water's flow path. These results allow for a greater understanding of how hydrology influences As and U occurrence in surface water and groundwater and can be used to help better predict areas at high risk for As and U contamination.