Global croplands, pastures, and human settlements have expanded in recent decades. This is accompanied by large increases in energy, water, and fertilizer consumption, along with considerable losses of biodiversity. In sub-Saharan Africa, policies are implemented without critical consideration; e.g., agricultural expansions impair ecosystem services. We studied land use/cover and the associated rate of change for four time epochs, i.e., 1991, 2001, 2011, and 2021. This employed remote sensing and GIS techniques for analysis, while future projections were modeled using cellular automata and the Markov chain. The kappa coefficient statistics were used to assess the accuracy of the final classified image, while reference images for accuracy assessment were developed based on ground truthing. Overall change between 1991 and 2021 showed that major percentage losses were experienced by water, forest, woodland, and wetland, which decreased by 8222 Ha (44.11%), 426,161 Ha (35.72%), 399,584 Ha (35.01%), and 105,186 Ha (34.82%), respectively. On the other hand, a percentage increase during the same period was experienced in cultivated land, built-up areas, and grasslands, which increased by 659,346 Ha (205.28%), 11,894 Ha (159.93%), and 33,547 Ha (98.47%), respectively. However, this expansion of thirsty sectors has not reversed the increasing amount of water discharged out of the Kilombero River catchment. We recommend the promotion of agroforests along with participatory law enforcement and capacity building of local communities’ institutions.