This study aims to integrate groundwater geochemistry and mathematical modeling to determine the dominant geochemical processes and groundwater residence time within the Wilcox aquifer in the northern Gulf Coastal Plain. Groundwater samples were collected and analyzed for major ion chemistry, stable isotopes (18O, 2H, and 13C), and radioisotope 36Cl content. Geochemical modeling enabled the identification of major sources and sinks of solutes in the aquifer. A two-dimensional, finite-difference, numerical model was used to determine the deep groundwater flow rate and transport of 36Cl in the aquifer. Major ion chemistry shows a chromatographic pattern along the flow path in which a gradual increase of Na+ and decrease of Ca2+ and Mg2+ is evident. The most plausible inverse models in the downgradient section of the aquifer indicate that oxidation of organic matter (OM), which may be associated with discontinuous lenses of lignite, and consequent release of CO2 sustain the reduction of Fe(III) (oxyhydr)oxides and sulfate and the dissolution of carbonate minerals (calcite and, in some instances, siderite). These processes, in turn, result in pyrite precipitation and exchange of Ca2+ for Na+ on clay-mineral surfaces. Models constrained with 13C are consistent with mole transfers between pairs of wells in close proximity, but not for the entire flow path. The observed range of δ13C of dissolved inorganic carbon (-7.3‰ to -12.4‰) is interpreted as a result of both oxidation of OM and dissolution of carbonates. Calculated values of 36Cl/Cl show an abrupt discontinuity between the upgradient and downgradient sections that was also observed in δ18O and δ2H data. The gradual enrichment of 18O and 2H along the flow path could be the result of diffusion. The distinct differences in δ18O and δ2H between the upgradient and downgradient Wilcox aquifer suggest that the latter preserves a paleoclimatic signal.