Climate change impact on water resources has been observing in Ukraine since the end of the 20th century. For now, only large-scale climate impact studies cover Ukraine territory, having low credibility for a specific catchment. This study aims to calculate future changes in river discharge, water flow components, and soil water within the Desna basin and evaluate vulnerability trends on this basis. The framework assembles the process-based SWAT (Soil and Water Assessment Tool) model and eight high-resolution regional climate models (RCMs) driven by RCP4.5 and RCP8.5 emission scenarios. The climate models are provided by the Euro-CORDEX initiative and based on three RCMs (RCA4, HIRHAM5, and RACMO22E) forced by five general circulation models (CNRM-CM5, EC-EARTH, IPSL-CM5A-MR, HadGEM2-ES, and MPI-ESM-LR). The results preferably show a moderate increase in the annual discharge till the end of the 21st century. The intra-annual changes of water balance components negatively affect the vegetation period because of higher dryness and temperature stress but reduce flood risk, diffuse pollution, and water erosion in the far future. In the river basin management plan, the highest attention should be paid to adaptive strategies in agriculture because of possible water deficit in the vegetation season under future climate scenarios.