Radium (Ra) is a geogenic radioactive contaminant that frequently occurs at elevated levels in the Midwestern Cambrian-Ordovician aquifer system (MCOAS). Geochemical indicators (e.g., redox conditions or total dissolved solids) can broadly characterize conditions associated with elevated Ra levels in groundwater, but do not consistently correlate to elevated Ra within specific stratigraphic horizons. A coupled geochemical and isotopic study of groundwater and aquifer solids for major and trace elements, Ra, and uranium (U) at discrete intervals in the MCOAS was used to elucidate processes that may be responsible for this disconnect, via analysis of groundwater as well as extracted and digested solid aquifer samples. We find that the potential for Ra mobilization varies by stratigraphic unit, as observed by whole-rock ²²⁶Ra/²³⁸U (dis)equilibrium. Overall, the examined aqueous geochemical characteristics (e.g., redox conditions, total dissolved solids) do not explain Ra concentrations within the system, suggesting that alternative factors, like solid-phase associations or the extent of alpha recoil damage, may be more important. A relation between aqueous ⁸⁷Sr/⁸⁶Sr and ²²⁶Ra suggests that minerals with radiogenic ⁸⁷Sr/⁸⁶Sr are more likely to release ²²⁶Ra to the aqueous system. Overall, the release of U and Ra due to water-rock interaction varies with discrete stratigraphy, depending on aqueous geochemistry and available mineral associations. Due to complex Ra-rock interactions and the heterogeneous geology of the MCOAS, aqueous geochemistry does not fully predict the mobilization and concentration of Ra in groundwater. As sources and sinks of Ra within the MCOAS vary across stratigraphy, knowledge of aqueous geochemistry, available solid-phase associations, and nuclide leachability all are important to consider for understanding elevated Ra occurrence in aquifer systems.