Villages within the Luki Biosphere Reserve and the surrounding cities have undergone rapid demographic growth and urbanization that have impacted the reserve’s natural landscape. However, no study has focused on the spatiotemporal analysis of its land use/land cover. The present research aims at providing a comprehensive analysis of land use/land cover change in the Luki Biosphere Reserve from the year 1987 to 2020, and to predict its future change for the year 2038. Landsat images were classified in order to provide land use/land cover maps for the years 1987, 2002, 2017 and 2020. Based on these maps, change detection, gradient direction, and landscape metric analyses were performed. In addition, land use/land cover change prediction was carried out using the Multilayer Perceptron Markov model. The results revealed significant land use/land cover changes in the Luki Biosphere Reserve during the study period. Indeed, tremendous changes in the primary forest, which lost around 17.8% of its total area, were noted. Other classes, notably savannah, secondary forest, built-up area, fallow land and fields had gained 79.35, 1150.36, 67.63, 3852.12 hectares, respectively. Based on the landscape metric analysis, it was revealed that built-up areas and fallow land and fields experienced an aggregation trend, while other classes showed disaggregation and fragmentation trends. Analysis further revealed that village expansion has significantly affected the process of land use/land cover change in the Luki Biosphere Reserve. However, the prediction results revealed that the primary forest will continue to increase while built-up area, fallow land and fields will follow a trend similar to a previous one. As for secondary forest and savannah, the forecast revealed a decrease of the extent during the period extending from 2020 to 2038. The present findings will benefit the decision makers, particularly in the sustainable natural resources management of the Luki Biosphere Reserve.