The improvement of water management requires monitoring techniques that accurately evaluate water quality status and detect the effects of land use changes on water chemistry. This study aimed to evaluate how multivariate statistical methods and water quality indices can be applied together to evaluate the processes controlling water chemical composition and the overall water quality status of a tropical watershed. Thirty-four water samples were collected in the Formoso River basin, located on the border of the Amazon Forest. Water parameters were measured in situ using a multiparameter and in the lab using spectroscopic and volumetric techniques. The water quality dataset was interpreted through principal component analysis, multivariate linear regression, and water quality indices. Statistical methods allowed us to identify the sources and geochemical processes controlling water quality chemistry, which were carbonate dissolution, runoff/erosion, nutrient input due to anthropogenic activities and redox reactions in flooded zones. They were also used to create linear functions to evaluate the effects of land use changes on the geochemical processes controlling water chemistry. Conversely, the water quality indices provide information about the overall condition of the water. The Weight-Arithmetic Quality Index correctly evaluates water suitability for its multiple uses, according to the Brazilian guidelines. Conversely, the Ontario Water Quality Index is not suitable to evaluate the water quality of tropical rivers, since the usual higher water temperature and the low oxygen contents associated with tropical environments result in biased water quality evaluations by this index.