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The process of knowledge production, dissemination and consumption has captured much scholarly attention from a political viewpoint in recent times. Discourses on development, empowerment, transformation and democracy have revolved around knowledge and power and more precisely on the politics of knowledge. Institutions of higher learning, especially universities, globally, as nerve centres of knowledge production and distribution, have not been spared from the challenges of the politics of knowledge. In this conceptual paper, we theorise the dynamics of the challenges and opportunities of the politics of knowledge in the context of the postcolonial African university’s endeavour to transform epistemologies in higher education in the 21 st century Africa. Our case is premised on three claims, namely that 1) the production and mediation of knowledge is a genuinely political process (Weiler, 2011b) 2) universities can be considered among the most political institutions in society (Ordorika, 1999) and 3) recontextualisation and transformation of university epistemologies (Weiler, 2011a) is a prerequisite for an authentic postcolonial African university.