Abstract In this paper, the responses of hydro-meteorological drought to changing climate in the Be River Basin located in Southern Vietnam are investigated. Climate change scenarios for the study area were statistically downscaled using the Long Ashton Research Station Weather Generator tool, which incorporates climate projections from Coupled Model Intercomparison Project 5 (CMIP5) based on an ensemble of five general circulation models (Can-ESM2, CNRM-CM5, HadGEM2-AO, IPSL-CM5A-LR, and MPI-ESM-MR) under two Representative Concentration Pathway (RCP) scenarios (RCP4.5 and RCP8.5). The Soil and Water Assessment Tool model was employed to simulate streamflow for the baseline time period and three consecutive future 20-year periods of 2030s (2021–2040), 2050s (2041–2060), and 2070s (2061–2080). Based on the simulation results, the Standardized Precipitation Index and Standardized Discharge Index were estimated to evaluate the features of hydro-meteorological droughts. The hydrological drought has a 1-month lag time from the meteorological drought and the hydro-meteorological droughts have negative correlations with the El Niño Southern Oscillation and Pacific Decadal Oscillation. Under the climate change impacts, the trends of drought severity will decrease in the future; while the trends of drought frequency will increase in the near future period (2030s), but decrease in the following future periods (2050 and 2070s). The findings of this study can provide useful information for the policy- and decisionmakers for a better future planning and management of water resources in the study region.