The quality of groundwater resources in the Pra Basin (Ghana) is threatened by ongoing river pollution from illegal mining. To date, there are very limited data and literature on the hydrochemical characteristics of the basin. For the first time, we provide regional hydrochemical data on surface water and groundwater to gain insight into the geochemical processes and quality for drinking and irrigation purposes. We collected 90 samples from surface water (rivers) and groundwater (boreholes) and analysed them for their chemical parameters. We performed a water quality assessment using conventional water quality rating indices for drinking water and irrigation. Cluster and factor analysis were performed on the hydrochemical data to learn the chemical variations in the hydrochemical data. Bivariate ion plots were used to interpret the plausible geochemical processes controlling the composition of dissolved ions in surface water and groundwater. The water quality assessment using Water Quality Index (WQI) revealed that 74% of surface water and 20% of groundwater samples are of poor drinking quality and, therefore, cannot be used for drinking purposes. For irrigation, surface water and groundwater are of good quality based on Sodium Adsorption Ratio (SAR), Wilcox diagram and United States Salinity (USSL) indices. However, Mn and Fe (total) concentrations observed in most surface water samples are above the acceptable limit for irrigation and therefore require treatment to avoid soil acidification and loss of availability of vital soil nutrients. Manganese and iron (total) are identified as the main contaminants affecting the basin’s water quality. The hierarchical cluster analysis highlights the heterogeneity in the regional hydrochemical data, which showed three distinct spatial associations based on elevation differences. Groundwater composition chemically evolves from a Ca–${\mathrm{HCO}}_3$ to a Na–${\mathrm{HCO}}_3$ and finally to a Na–Cl water type along the flow regime from the recharge to the discharge zone. The bivariate ion plot and the factor analysis underscore silicate weathering, carbonate dissolution and ion exchange as the most likely geochemical processes driving the hydrochemical evolution of the Pra Basin groundwater. Going forward, geochemical models should be implemented to elucidate the dominant reaction pathways driving the evolution of groundwater chemistry in the Pra Basin.