The Nyabarongo river catchment in Rwanda has experienced significant changes in its land use and land cover (LULC) in recent decades, with profound implications for non-point source pollution. However, there are limited studies on non-point pollution caused by nutrient loss associated with land use and land cover changes in the catchment. This study investigates the spatiotemporal impacts of these changes on water quality considering nitrogen and phosphorus within the catchment from 2000 to 2020 and 2030 as a projection. The SWAT model was used in analysis of hydrological simulations, while the CA–Markov model was used for the future projection of LULC in 2030. The results revealed (1) the important changes in LULC in the study area, where a decrease in forestland was observed with a considerable increase in built-up land, grassland, and cropland; (2) that the R2 and NSE of the TN and TP in the runoff simulation in the catchment were all above 0.70, showing good applicability during calibration and validation periods; (3) that from 2000 to 2020 and looking to the projection in 2030, the simulated monthly average TN and TP levels have progressively increased from 15.36 to 145.71 kg/ha, 2.46 to 15.47 kg/ha, 67.2 to 158.8 kg/ha, and 9.3 to 17.43 kg/ha, respectively; and (4) that the most polluted land use types are agriculture and urban areas, due to increases in human activities as a consequence of population growth in the catchment. Understanding the patterns and drivers of these changes is critical for developing effective policies and practices for sustainable land management and protection of water resources.