As COVID-19 vaccine acquisition and deployment accelerates, tensions also increase. This review aims to identify and understand the significance of population attitudes toward COVID-19 vaccines in Africa. A systematic review was conducted. Searches were conducted in MEDLINE, CINAHL, EMBASE, and Global Health databases. Database searches began on June 23, 2021, and the last search date was June 30, 2021. The methodological quality of the studies included in this review was assessed using the Mixed methods appraisal tool. A total of 609 articles were retrieved, and 23 met the eligibility criteria. All 23 included studies were cross-sectional. Three attitudes were identified: acceptance, reluctance, and refusal to be vaccinated. Acceptance of vaccination was motivated by confidence in the accuracy of the government’s response to COVID-19 and the fact that relatives had been diagnosed with or died from COVID-19. Reluctance was based on fear of vaccine quality and side effects, and insufficient clinical trials. Finally, refusal to be vaccinated was justified by reasons such as the unreliability of clinical trials and insufficient data regarding the vaccine’s adverse effects. This review revealed common attitudes of African populations toward COVID-19 vaccines. The results indicate that research needs to focus more on identifying facilitators of COVID-19 vaccination. However, they also provide essential elements for health personnel in charge of vaccination to develop strategies to achieve satisfactory coverage rates.