With a population of 1.3 billion people, of which 56% reside in rural settings, Africa seemed ill-prepared to handle the distribution of a COVID-19 vaccine. In addition, the capacity needed for a successful COVID-19 vaccination campaign in Africa surpassed the available resources in local and state health agencies. As a result, African governments were advised to coordinate resources, health officials, and vaccinators, including local health practitioners, medical technicians, and pharmacists for the largest-ever vaccination campaign in Africa. Although the rolling out of the SARS-COV-2 vaccine was, as expected, slow in many African countries, and not yet enough to cover the entire population in Africa, the mass vaccination campaign in Africa must continue to ensure that priority for vaccination is extended beyond front-liners (healthcare workers) and specific high-risk populations, which has largely been the case in some African countries. This article highlights the overarching areas that we believe need to be prioritized to enhance Africa's effectiveness and coverage in the mass COVID-19 vaccination program.