Inverse geochemical modeling from PHREEQC, and multivariate statistical methods were jointly used to define the genetic origin of chemical parameters of groundwater from the Voltaian aquifers in the Afram Plains area. The study finds, from hierarchical cluster analysis that there are two main hydrochemical facies namely the calcium-sodium-chloride-bicarbonate waters and the magnesium-potassium-sulfate-nitrate waters in the northern and southern sections, respectively, of the Afram Plains area. This facies differentiation is confirmed by the distribution of the SO(4)(2-)/Cl(-) ratio, which associates groundwater from the northern and southern sections to areas influenced by contact with evaporites and seawater, respectively. Principal component analysis (PCA) with varimax rotation using the Kaiser criterion identifies four principal sources of variation in the hydrochemistry. Mineral saturation indices calculated from both major ions and trace elements, indicate saturation-supersaturation with respect to calcite, aragonite, k-mica, chlorite, rhodochrosite, kaolinite, sepiolite, and talc, and undersaturation with respect to albite, anorthite, and gypsum in the area. Inverse geochemical modeling along groundwater flowpaths indicates the dissolution of albite, anorthite and gypsum and the precipitation of kaolinite, k-mica, talc, and quartz. Both the PCA and inverse geochemical modeling identify the incongruent weathering of feldspars as the principal factors controlling the hydrochemistry in the Afram Plains area. General phase transfer equations have been developed to characterize the geochemical evolution of groundwater in the area. A very good relationship has been established between calcite and aragonite saturation indices in the Afram Plains area, with R(2)=1.00.