This study analyzed the reported incidence of COVID-19 and associated epidemiological and socio-economic factors in the WHO African region. Data from COVID-19 confirmed cases and SARS-CoV-2 tests reported to the WHO by Member States between 25 February and 31 December 2020 and publicly available health and socio-economic data were analyzed using univariate and multivariate binomial regression models. The overall cumulative incidence was 1846 cases per million population. Cape Verde (21350 per million), South Africa (18060 per million), Namibia (9840 per million), Eswatini (8151 per million) and Botswana (6044 per million) recorded the highest cumulative incidence, while Benin (260 per million), Democratic Republic of Congo (203 per million), Niger (141 cases per million), Chad (133 per million) and Burundi (62 per million) recorded the lowest. Increasing percentage of urban population (beta=-0.011, p=0.04) was associated with low cumulative incidence, while increasing number of cumulative SARS-CoV-2 tests performed per 10000 population (beta=0.0006, p=0.006) and proportion of population aged 15-64 years (adjusted beta=0.174, p<0.0001) were associated with high COVID-19 cumulative incidence. With limited testing capacities and overwhelmed health systems, these findings highlight the need for countries to increase and decentralize testing capacities and adjust testing strategies to target most at-risk populations.