This study aimed to assess the impacts of future development and climate change on the water balance in the Upper Srepok River Basin, in the Central Highlands of Vietnam. A hydrological model was calibrated and validated to model the rainfall-runoff process. Estimates of the water demand of different water sectors were based on the functional relationships between water and productive uses. The estimates were input into a calibrated basin management model for simulation. The climate projections were downscaled to the studied basin. Future land use was predicted using a geographic information system (GIS)-based logistic regression approach. The water balance was examined under various developed scenarios. The results show a relatively high current annual irrigation water deficit at a basin scale; some sub-basins suffer from water shortage, especially during dry seasons and dry years. All water use sectors will be affected to some extent under the impacts of future development and water supply policies. When the new water policy is introduced, the deficits of irrigation and environmental flow are reduced while the power deficit is increased. Considering climate change impact, the annual water deficits are reduced. However, the temporal and spatial variations of rainfall make future water deficits more severe during the dry seasons and dry years.