The 3S Rivers are a major tributary system to the Mekong River, and geographically defined by three major rivers: the Sekong, Sesan, and Srepok. The 3S river basins spread over approximately 78,650 m2, whose area is located 33% in Cambodia, 29% in Laos (29%), and 38% in Vietnam. The basins are widely recognized for their biological importance, rich ecosystems and key fish migration routes. These international rivers are witnessing a trend of competition with focus on the use of each country’s water resources for its own development needs coupled with potential consequences and challenges for other countries. The changes of climate have vital impacts on water resources in the 3S River Basins. Therefore, it is necessary to estimate such impacts and their consequences on hydrological processes in the regions. In this study, we applied an in-house hydrologic modeling platform, the Seoul National University Watershed Simulation Tool (SNU-WS) to evaluate the impacts of climate change on streamflow in 3S River Basins for near (2021-2040), middle (2041-2060), and far future periods (2061-2080) and (2081-2100). The future climate change scenarios were downscaled from 19 different GCMs, under the medium (RCP4.5) and high emissions scenario (RCP8.5), using the stochastic weather generator (LARS-WG). The climate in this area would generally become warmer and wetter under both emission scenarios. The streamflow is predicted to be increased in the wet season and decreased in the dry season; and the expected annual change in streamflow in Srepok, Sesan and Sekong are -1.0, 6.5 and 1.5 percentages, respectively. Consequently, an average annual change in streamflow of the 3S Rivers is about 1.0%. The result obtained from this study can provide useful reference to analyze, evaluate and utilize for water resource management of the transboundary river systems under the effects of climate changes.