Over the past few decades, the growth of population and the development of the economy have had a significant impact on the way land is used and covered (LULC) in the Nile Nyabarongo River basin. However, there is limited knowledge about the patterns of land use and the mechanisms that drive changes in these patterns because of human activities. Therefore, it is crucial to examine how land use and cover are shifting in this area, identify the factors responsible for these changes, and forecast future patterns. This study sought (1) to evaluate the changes in LULC from 1990 to 2020 and (2) to predict future fluctuations until 2060. By analyzing the LULC data for the years 1990, 2000, 2010, and 2020, this study simulated the future LULC patterns of the area for the next 30 years using the LULC transition matrix and the Markov chain model. The study classified the LULC into five categories: forestland, grassland, cropland, settlement, and water. The results revealed that there will be significant changes in the LULC of the study area from 2030 to 2060. The forest area is projected to decrease by 801.7 km, 771.6 km, and 508.2 km, while the cropland area will expand by 6307.2 km, 6249.2 km, and 6420.6 km during this period. The grassland area will experience a small increase of 761.1 km, 802.4 km, and 859.1 km, and the settlement area will also grow by 355.2 km, 407.4 km, and 453.2 km. In contrast, the water area will decrease by 55.9 km, 50.5 km, and 40 km. The ongoing pattern of LULCC is expected to persist over the next three decades, with an increase in cropland area and grassland. This study’s findings can provide valuable insights for land use planners and water resource managers in developing fair land use and water resource management policies for the entire region, enabling them to make well-informed decisions.