The effects of climate and land-use changes have put intense pressures on water resources with regard to water quantity and quality in the La Buong River Basin, located in Southern Vietnam. Therefore, an estimate of such effects and their consequences on water resources in this area is needed. The aim of this study is to evaluate the segregated and aggregated effects of climate change and land-use change on streamflow and water quality components (sediment and nutrient loads) using the well-known Soils and Water Assessment Tool (SWAT). The SWAT model was carefully calibrated and validated against the observation data before it can be used as a simulation tool to study the impacts of climate and land-use changes on hydrological processes. As a result of this study, it shows a reduction in the wet-season and annual streamflow, and sediment and nutrient loads will be occurred in the study area due to climate change effects, while the streamflow, and sediment and nutrient loads will be increased under the effects of the land-use change. Moreover, the streamflow and water quality components are more sensitive to land-use change than climate change. The results obtained from this study can provide a basic knowledge of the effects of climate and land-use changes on the streamflow and water quality to the local and national authorities for the future development of integrated water resources management in the La Buong River Basin.