This work reports a geochemical study of three watersheds located in the upper course of the Paracatu River (one of the most important sub-basins of the upper-middle São Francisco River). It aimed to establish a geochemical model that can assist in identifying the sources and distribution of physico-chemical components and dissolved metals in water, assessing how the local geology and human activities influence the quality of the aquatic systems. The predominant geology of the region includes the Vazante Group, basically formed by a sequence of clay and dolomitic clay where zinc and lead mineralization occurs, and the Canastra Group (Paracatu Formation) composed of a sequence of phyllites and carbonaceous phyllites with intercalations of quartzites, where gold occurs in iron and arsenic sulfides. The samples were analysed using ICP/OES, AAS, spectrophotometric (UV/Visible) techniques and volumetric methods. The development of the geochemical model used multivariate statistical analysis including principal components, multiple regression and hierarchical clustering. The proposed model determined that Fe, Mn, SO42-, and color come primarily from sulfide oxidation; HCO3-, Ca, Mg, Zn, and Ba, from dolomitic limestone dissolution, and PO43-, NO3-, NH3 and turbidity from the input of urban sewage. Indices were created for each group of parameters representing the intensity of these processes and classifying the sampling sites according to their predominant chemical composition (water with low mineralization, high carbonate, or sulphate mineralization and pollution by urban sewage). The proposed model can be used in regional water quality monitoring, and as a reference for other locations.