Changes in land use and land cover usually affect the hydrological processes of river flows, sediment transport, and water quality on a global scale. Hence, the objective of this paper was to investigate the effect of Land Use Land Cover (LULCC) on the Hydrology of Rwizi River Catchment located in South-western Uganda using appropriate standard techniques and procedures including Soil and Water Assessment Tool (SWAT). Model calibration and validation demonstrated good agreement (R² = 0.76-0.86, NSE = 0.75-0.78). LULC analysis revealed significant increases in built-up areas and forestland, with declines in grazing land and wetlands. These changes were driven by socio-economic factors and hydro-climatic influences. The study found strong correlations between LULC types and sediment yield, highlighting the implications for water quality and erosion control. The results show that urban growth raises surface runoff and peak flows as a result of a rise in impervious surfaces, whereas agricultural intensification raises water demand and lowers base flow, especially during dry spells. Deforestation has led to increased sedimentation rates, degrading water quality. These findings underscore the significant anthropogenic and climatic impacts on LULCC dynamics and hydrological processes in the catchment. The study emphasizes the critical need for integrated watershed management strategies to mitigate these impacts and ensure sustainable water management practices. By advancing understanding in hydrological sciences, this research informs policy and management decisions for sustainable development in tropical river basins globally.