Africa is the second largest continent and has its socioeconomic and health peculiarities. Countries are faced with varying challenges towards its Universal Health Coverage (UHC) achievement and hence the region requires health system reforms to drive equitable and balanced medical services to its populace. The main objectives of the paper were to explore the complexities of the African health systems, subsequently highlighting major challenges to UHC and to provide a framework for strategic approaches to health system strengthening to ensure realization of UHC. Information presented in this paper was collected from published literature and reports on Rwanda, Kenya, Nigeria, Tanzania, Ghana, Tunisia, Democratic Republic of Congo, Zambia, Egypt and South Africa, amidst other African countries. The published literature points to the presence of a somewhat slow progress towards UHC or at least an existent knowledge of it. However, common challenges faced can be grouped into 1) Financial constraints which include low levels of government expenditure on health and increased out-of-pocket percentages, (2) Lack of coverage of key services which includes majorly immunization rates and existence of health insurance for citizens, (3) Input constraints ranging from drug availability to skilled healthcare workforce, information and research and (4) Lack of political support and commit-ment towards universal health coverage. To overcome the above-stated constraints, two broad groups of interventions were identified; General interventions largely focusing on reprioritization of health budget, quality and improved services, equipped facilities and efficient social protection systems; and Specific interventions which emphasizes the importance of eliminating shortage of health workers, ensuring availability of essential medicines/ products, embracing decen-tralization at supply chain management, validating data/ information system and advocacy for impactful health education/promotion. Although there will be strength and weakness for what-ever reforms adopted, implementation is totally contextual and contingent upon countries' specific health system bottlenecks.