Groundwater quality of the Banana Plain (Mbanga, Njombe, Penja-Cameroon) was assessed for its suitability for drinking, domestic, and agricultural uses. A total of 67 groundwater samples were collected from open wells, springs, and boreholes. Samples were analyzed for physicochemical properties, major ions, and dissolved silica. In 95% of groundwater samples, calcium is the dominant cation, while sodium dominates in 5% of the samples. Eighty percent of the samples have HCO(3) as major anion, and in 20%, NO(3) is the major anion. Main water types in the study area are CaHCO(3), CaMgHCO(3), CaNaHCO(3), and CaNaNO(3)ClHCO(3). CO(2)-driven weathering of silicate minerals followed by cation exchange seemingly controls largely the concentrations of major ions in the groundwaters of this area. Nitrate, sulfate, and chloride concentrations strongly express the impact of anthropogenic activities (agriculture and domestic activities) on groundwater quality. Sixty-four percent of the waters have nitrate concentrations higher than the drinking water limit. Also limiting groundwater use for potable and domestic purposes are contents of Ca(2+), Mg(2+) and HCO(3) (-) and total hardness (TH) that exceed World Health Organization (WHO) standards. Irrigational suitability of groundwaters in the study area was also evaluated, and results show that all the samples are fit for irrigation. Groundwater quality in the Banana Plain is impeded by natural geology and anthropogenic activities, and proper groundwater management strategies are necessary to protect sustainably this valuable resource.