The Pra Basin in Ghana is well-known for its abundant mineral resources, dense forest coverage, and fertile soil. The region faces major water management challenges due to illegal mining practices, resulting in surface water pollution and necessitating groundwater use as an alternate water source. Unfortunately, there is limited information available regarding the chemical characteristics of groundwater in the region, posing challenges for water management. This study examined the quality, hydrochemical variability and geochemical processes driving the chemical evolution of the groundwater. Samples of surface water and groundwater were collected and analyzed for chemical parameters. We employed multivariate statistics, including cluster and factor analysis, to identify regional variations and interrelationships among the parameters. The resulting clusters were used to formulate a hypothetical groundwater flow path to model the geochemical reactions that control the groundwater composition using combinatorial inverse modelling based on the local thermodynamic equilibrium hypothesis. The weathering of silicate minerals, including albite, anorthite, chalcedony, and k-feldspar, was found to be the dominant process driving the groundwater's chemical evolution. Models adequately predicted the composition of groundwater along the flow path and serve as a guide for the development of sustainable water resource management strategies for the catchment. Overall, our modelling approach presented here can be useful in regions with large variability in water chemistry and limited knowledge of aquifer mineralogy.