The hydrogeochemical evolution and quality assessment of groundwater within the transboundary Atankwidi basin have been carried out in Ghana. Various hydrochemical models and scenarios were employed to ascertain the possible sources, mechanism of mobilization, andthe processes controlling groundwater chemistry from points of recharge to areas of discharge. Analysis of twenty-six (26) groundwater samples showed that all parameters fell within acceptable limits for drinking water except fluoride, conductivity, and total hardness. The dominance of cations and anions was in the order Na ˃ Ca ˃ Mg ˃ K and HCO₃ ˃ SO₄ ˃ Cl⁻ ˃ F⁻ ˃ PO₄⁻ ˃ NO₃. Four groundwater types were identified—Ca-Na-Mg-HCO₃ ˃ Na-Ca-Mg-HCO₃ ˃ Na-Ca-HCO₃ ˃ Ca-Na-HCO₃. The major source of chemical evolution in groundwater was water-rock interaction (silicate minerals) with infiltrating carbonic acid as the agent of weathering resulting in the release of Na, Ca, K, and HCO₃⁻. Cationic exchange between alkali metals and alkaline earth metals is the main chemical process altering groundwater chemistry, resulting in mobilization of Ca and the consumption of Na at favorable sites as groundwater approaches discharge points. There is possibly little or insignificant contribution from anthropogenic factors to the build-up of groundwater chemistry in the study area.