The Birimian and Tarkwaian aquifer systems are the main sources of water supply for the Bosome Freho District and Bekwai Municipality inhabitants in the Ashanti region of Ghana. A hydrogeochemical assessment was carried out to ascertain the natural baseline chemistry of the groundwaters and the factors influencing groundwater chemistry in these two areas. A multivariate statistical tool consisting of principal component analysis (PCA) and hierarchical cluster analysis (HCA) together with hydrochemical graphical plots was applied on 64 groundwater samples. The Q–mode HCA results were used to explain the groundwater quality flow paths where three spatial groundwater zones and water types were delineated. The first type consists of Ca–Mg–HCO3 freshwater (recharge zone), which transitions into Ca–Na–HCO3 or Na–Ca–HCO3 mixed waters (intermediate zone) and finally evolve to the third type of Na–Ca–Mg–HCO3–Cl water (discharge zone). The study also reveals that the natural process influencing water chemistry is groundwater–rock interaction from carbonate and silicate weathering/dissolution, aided by carbonic acid from precipitation and releases concentration of Na+, Ca2+, Mg2+ and HCO3- into the groundwaters significantly. The chloro-alkaline indices also reveal cation exchange as the principal natural factors that control groundwater chemistry in the area. Anthropogenic activities have little influence on groundwater chemistry. The quality of groundwater in the Bosome Freho District and Bekwai Municipality are suitable for irrigational use and drinking water consumption. The results obtained so far will contribute to research paucity in the study area and serve as a guide for decision-makers for improved water resources management.