This study summarizes progress made in rolling out COVID-19 vaccinations in the African region in 2022, and analyzes factors associated with vaccination coverage. Data on vaccine uptake reported to the World Health Organization (WHO) Regional Office for Africa by Member States between January 2021 and December 2022, as well as publicly available health and socio-economic data, were used. A negative binomial regression was performed to analyze factors associated with vaccination coverage in 2022. As of the end of 2022, 308.1 million people had completed the primary vaccination series, representing 26.4% of the region’s population, compared to 6.3% at the end of 2021. The percentage of health workers with complete primary series was 40.9%. Having carried out at least one high volume mass vaccination campaign in 2022 was associated with high vaccination coverage (β = 0.91,p< 0.0001), while higher WHO funding spent per person vaccinated in 2022 was correlated with lower vaccination coverage (β = −0.26,p< 0.03). All countries should expand efforts to integrate COVID-19 vaccinations into routine immunization and primary health care, and increase investment in vaccine demand generation during the transition period that follows the acute phase of the pandemic.