The aim of this study is to examine uncertainty in projections of streamflow and water quality (TSS load) under the impact of changing climate in the Dong Nai River Basin, which is one of most vulnerable areas to climate change in Vietnam. Uncertainty associated with different general circulation models (CanESM2, CNRM-CM5, HadGEM2-AO, ISPL-CM5A-LR, and MPI-ESM-MR), emission scenarios (RCP4.5 and RCP8.5), statistical downscaling techniques (delta change method, SDSM, and LARS-WG), and hydrological models (SWAT and HSPF) was considered. The results indicate that the largest uncertainty source is come from GCMs simulations, followed by the emission scenarios, statistical downscaling methods, and hydrological models. Consequently, it should pay more attention to apply different GCMs when implementing studies on the hydrological impact of changing climate.