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The emergence of COVID-19 virus at the onset of the year 2020 brought a global catastrophe, with countries that have the strongest health delivery systems being some of the hardest hit. With the cure seemingly not in sight, nations have pinned their hopes on the development of vaccines. Whilst most developed nations have embarked on mass vaccination of citizens, largely due to their ability to manufacture vaccines, the African continent has lagged behind. This paper, which is based on literature and documentary survey, explores the implications of African beliefs and related factors on the uptake of the COVID-19 vaccines, as well as articulating on how the governments can avert the consequences of belief guided negative perceptions on successful rollout of the COVID- 19 vaccination. The paper reveals that religious and cultural beliefs that do not subscribe to vaccination are the main drivers to vaccine hesitancy. Conspiracy theories surrounding the origins of the COVID-19 virus and social media misinformation have also heightened suspicion and mistrust over the efficacy of the vaccines. The paper recommends mass public awareness, community engagement, countering misinformation and exemplary leadership as prescriptive measures for vaccine hesitancy in Africa.