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Ugandan rivers are being tapped as a resource for the generation of hydropower in addition to other uses. Studies on the reliability of these hydropower plants due to climate and land-use/land cover changes on the hydrology of these rivers are scanty. Therefore, this study aimed to model the impact of the changing climate and land-use/cover on hydropower reliability to aid proper planning and management. The hydropower reliability of Muzizi River catchment was determined from its past (1998–2010) and midcentury (2041–2060) discharge at 30 and 95% exceedance probability under Representative Concentration Pathways (RCPs) of 4.5 and 8.5, respectively. The past and projected hydropower were compared to determine how future climate and land-use changes will impact the discharge and hydropower reliability of Muzizi River catchment. Six LULC scenarios (deforestation, 31–20%; grassland, 19–3%; cropland, 50–77%; water bodies, 0.02–0.01%; settlement, 0.23–0.37%, and Barren land 0.055–0.046% between 2014 and 2060) and three downscaled Regional Climate Model (REMO and RCA4 for precipitation and RACMO22T for temperature from a pool of four CORDEX (Coordinated Regional Climate Downscaling Experiment) Africa RCMs) were examined. A calibrated SWAT simulation model was applied for the midcentury (2041–2060) period, and a potential change in hydropower energy in reference to mean daily flow (designflow ≥ 30% exceedance probability), firm flow (flow ≥ 95% exceedance probability), and mean annual flow was evaluated under the condition of altered runoff under RCP4.5 and RCP8.5 climate change scenarios for an average of REMO and RCA4 RCM. The future land use (2060) was projected using the MOLUSCE (Module for Land Use Change Evaluation) plugin in QGIS using CA-ANN. Three scenarios have been described in this study, including LULC change, climate change, and combined (climate and LULC change). The results suggest that there will be a significant increase in annual hydropower generation capacity (from 386.27 and 488.1 GWh to 867.82 and 862.53 GWh under RCP4.5 and RCP8.5, respectively) for the combined future effect of climate and land-use/cover changes. Energy utilities need to put in place mechanisms to effectively manage, operate, and maintain the hydropower plant amidst climate and land-use change impacts, to ensure reliability at all times. HIGHLIGHTS Innovative approaches for hydrological modeling in data-scarce scenarios.; The possibility to utilize bias-corrected reanalysis and historical discharge data to build a climate model in data-scarce scenarios.; Sheds light on the potential risks of land-use and climate change on hydropower reliability in data scarcity areas.; Informs the need to implement prudent catchment management practices and develop policies.;