Mining of volumetrically small, but relatively enriched (average 0.6% U₃O₈) breccia pipe uranium (BPU) deposits near the Grand Canyon, Arizona, USA has the potential to affect groundwater and springs in the area. Such deposits also contain base metal sulfides that can oxidize to generate acid mine drainage and release trace metals. In this study, sequential batch experiments were conducted to simulate the geochemistry of local shallow groundwater that contacts BPU ore and then moves downgradient through sedimentary strata. The experiments simulated shallow groundwater in a carbonate aquifer followed by contact with BPU ore. The experiments subsequently simulated contact with sedimentary rocks and changing oxygen availability. Concentrations of several contaminants of potential concern became substantially elevated in the waters exposed to BPU ore, including As, Co, Ni, U, and Zn, and to a lesser extent, Mo. Of these, Co, Mo, Ni, and U were minimally attenuated by downgradient processes, whereas Zn was partially attenuated. Sb and Tl concentrations were more moderately elevated but also generally minimally attenuated. Although the mixture of elements is particular to these BPU ore deposits, sulfide oxidation in the ore and carbonate buffering of pH by sedimentary rocks generates patterns of water chemistry common in acid mine drainage settings. Ultimately, downgradient concentrations of elements sourced from BPU ore will also be strongly influenced by non-geochemical factors such as the quantities of water contacting BPU materials, heterogeneity of materials along flow paths, and mixing with waters that have not contacted BPU materials.