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Makerere University was for a long time, the focal point for literary activities that were central to African nationalist culture. However over time, its glory and reputation in teaching, publication, and scholarship, and her commitment to dissemination of scientific knowledge through research and other indicators that mirror global quality, have declined. Yet the determinants of the low performance of the university have not been determined from an empirical perspective. This study identified the determinants of performance and the effect of each determinant on the capacities of the academic staff to do research, publish, teach and carry out community service. Data was collected from 208 randomly selected academic staff; and analysed through thematic analysis, z-test, t-test, factor analysis and multiple regression analyses techniques. The study found the average performance to be 59.83%. Governance, administrative, personal, policy, education resources, and managerial factors are the major factors influencing performance and each respectively contributes 28.1%, 17.6%, 11.5% 13.8%, 11.2%; 7.5% to the variance in the performance. They account for 55.513% of the variance.