In this study, we investigated the impact of climate change on streamflow and water quality (TSS, T-N, and T-P loads) in the upper Dong Nai River Basin using the Soil and Water Assessment Tool (SWAT) hydrological model. The calibration and validation results indicated that the SWAT model is a reasonable tool for simulating streamflow and water quality for this basin. Based on the well-calibrated SWAT model, the responses of streamflow, sediment load, and nutrient load to climate change were simulated. Climate change scenarios (RCP 4.5 and RCP 8.5) were developed from five GCM simulations (CanESM2, CNRM-CM5, HadGEM2-AO, IPSL-CM5A-LR, and MPI-ESM-MR) using the delta change method. The results indicated that climate in the study area would become warmer and wetter in the future. Climate change leads to increases in streamflow, sediment load, T-N load, and T-P load. Besides that, the impacts of climate change would exacerbate serious problems related to water shortage in the dry season and soil erosion and degradation in the wet season. In addition, it is indicated that changes in sediment yield and nutrient load due to climate change are larger than the corresponding changes in streamflow.