Although there are numerous modeling tools available for managing water resources, they tend to focus on relatively small watersheds (<25,000 km²) and evidence is scarce regarding their applications to large watershed management and planning. The use of hydrological modeling tools in decision making is particularly challenging in large tropical countries such as Brazil. Here we tailored and customized SWAT (Soil and Water Assessment Tool) calibration, validation and sensitivity analysis for large Brazilian watersheds (>25,000 km²). Our results show that customized SWAT calibrations successfully simulated flow behaviors across the Rio das Velhas basin, which contains heterogeneous landforms and land uses. The multisite calibration method was adopted because of the large basin area and the availability of flow monitoring stations. As a result of the multi-site calibration, specific regionalized parameters were obtained for each group of sub-basins. Our results showed a good adjustment of the model. NS (Nash & Sutcliffe coefficient) values were 0.73 - 0.97 (calibration) and 0.51 - 0.98 (validation). PBIAS (% bias) was 11.3 to 19.4 (calibration) and -18.6 to 24.6 (validation) and R² values were >0.6 in all sub-basins. We conclude that hydrological models coupled with GIS facilitates simulating complex hydrological processes and can improve decision making by Brazilian water resource managers.