This study empirically examines the predictive relationship between Institutional Autonomy (IA) and Academic Freedom (AF) whilst controlling for the mediating effect of corporate governance (CG) amongst selected higher education institutions in Ghana. It also looks at the difference between females and males and their perceptions of the predictive relationship under the study. Using the explanatory research design, structured questionnaires were administered to 128 teaching and non-teaching staff of selected higher education institutions in Ghana. Structured equation modeling (SEM) via Smart PLS 4.0 was used for analyzing the research questions. The study finds that institutional autonomy is statistically significant in predicting academic freedom and corporate governance effectively mediates the predictive relationship between institutional autonomy and academic freedom. In order to create a viable environment for academic work and ingenuity to thrive, the management of higher education institutions should allow autonomy in areas such as organization, academics, finance and staffing in order to improve academic freedom. This study is founded on the theories of the academic oligarchy model, the stakeholder theory and the gender schema theory the study elucidates how corporate governance significantly mediates the predictive relationship between institutional autonomy and academic freedom within the context of higher education in Ghana.