In this study, we investigated the separate and combined impacts of climate and land-use changes on hydrological response in the Central Highlands of Vietnam during the period 1981-2009. The Mann-Kendall and Pettit tests were applied to detect the trends in the hydro-meteorological data. The Soil and Water Assessment Tool (SWAT) was setup in the region, and evaluation based on daily data highlights the models adequacy. From this, the responses of hydrology to climate variability and land-use changes were considered. Overall, variability in climate seems to strongly drive the variability in the hydrological response in comparison to alternations in the hydrological regime due to land-use change during the period 1981-2009. The results indicate that land-use change had a minor impact on the annual flow (0.4% reduction), whilst the impact from climate variability had been more significant (13.5% change). Under the impact of coupled climate variability and land-use change, the annual streamflow increased by 13.1%.