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The Upper Parana River Basin (UPRB) has undergone many rapid land use changes in recent decades, due to accelerating population growth. Thus, the prediction of water resources has crucial importance in improving planning and sustainable management. This paper presents a large-scale hydrological modelling of the UPRB, using the Soil and Water Assessment Tool (SWAT) model. The model was calibrated and validated for 78 outlets, over a 32-year simulation period between 1984 and 2015. The results and the comparison between observed and simulated values showed that after the calibration process, most of the outlets performed to a satisfactory level or better in all objective functions analyzed with 86%, 92%, 76%, 88%, and 74% for Percent bias, Coefficient of determination, Nash-Sutcliffe efficiency, Kling-Gupta efficiency, and the Ratio of Standard deviation of observations to root mean square error, respectively. The model output provided in this work could be used in further simulations, such as the evaluation of the impacts of land use change or climate change on river flows of the Upper Parana Basin.