Higher education in sub-Saharan Africa plays a critical role in meeting local and regional challenges yet still reaches a very small subset of the population. This case study focuses on Makerere University, the flagship university of Uganda, which is striving to make a difference locally and globally. It has survived colonialism, dictatorships, and economic disaster and has become one of the leading universities in Africa. Using the conceptual framework of U.S. landgrant higher education, this study seeks to analyze Makerere across the land-grant domains, focusing on tensions, facilitators, and barriers. The study consisted of interviews representing a diversity of stakeholders, field observation, and numerous documents and articles. Six major themes emerged including Makerere's aspiration to be a research-led institution, the impact of neoliberalism, challenges in undergraduate education, the importance of reputation and saga, the role of the Ugandan government, and the continuing effects of colonialism. These findings are discussed in relationship to the land-grant domains, and conclusions are shared.