Southeast Asia, in general, and the Mekong Basin (MB), in particular, with its typically warm and wet climate, face water resource challenges. A deep understanding of the future streamflow is needed to manage water resource suc-cessfully. Data scarcity and topographical differences have made it difficult to accurately reproduce the streamflow regime in the sub-catchment of the MB. The main goal of this study was to provide the first assessments of stream -flow impacts due to climate change for the Nam Ou Basin, a primary Lao sub-catchment of the MB, employing the most updated Couple Model Intercomparison Project Phase 6 (CMIP6) climate scenarios. The MIKE-NAM (Nedbor Affstromnings Model), the observed hydro-meteorological data, and the Moderate Resolution Imaging Spectroradiometer (MODIS) evaporation were employed. The climate change scenarios showed increases in sea-sonal and annual river discharges with different magnitudes in the future. The annual streamflow was expected to rise by 0.31%, 16.75%, and 38.31% in the 2040s as well as 23.35%, 32.80%, and 74.82% in the 2080s under three scenarios, respectively. The wet season in the Nam Ou Basin occurs one month earlier. The wet season flows increased by 5.6-76.9%, and the dry season flow showed a contrasting directional change, decreased by 8.4%. The annual peak discharge also exhibited an increase of 3.2-14.6% for the SSP1-1.9 scenario in the mid-century (the 2040s), and end-century (2080s). Those figures are 8.9-19.7% for the SSP2-4.5, and 23.3-48.9% for the SSP5-8.5 scenario, respectively. The study revealed the streamflow variation under the effect of climate change in the Nam Ou Basin, a sub-catchment of the MB, highlighting the need for special consideration in disaster risk mitigation, especially under climate change.