The World Health Organization African region recorded its first laboratory-confirmed coronavirus disease-2019 (COVID-19) cases on 25 February 2020. Two months later, all the 47 countries of the region were affected. The first anniversary of the pandemic occurred in a changed context with the emergence of new variants of concern (VOC) and growing COVID-19 fatigue. This study describes the epidemiological trajectory of COVID-19 in the region, summarises public health and social measures (PHSM) implemented and discusses their impact on the pandemic trajectory. As of 24 February 2021, the African region accounted for 2.5% of cases and 2.9% of deaths reported globally. Of the 13 countries that submitted detailed line listing of cases, the proportion of cases with at least one co-morbid condition was estimated at 3.3% of all cases. Hypertension, diabetes and human immunodeficiency virus (HIV) infection were the most common comorbid conditions, accounting for 11.1%, 7.1% and 5.0% of cases with comorbidities, respectively. Overall, the case fatality ratio (CFR) in patients with comorbid conditions was higher than in patients without comorbid conditions: 5.5% vs. 1.0% (P < 0.0001). Countries started to implement lockdown measures in early March 2020. This contributed to slow the spread of the pandemic at the early stage while the gradual ease of lockdowns from 20 April 2020 resulted in an upsurge. The second wave of the pandemic, which started in November 2020, coincided with the emergence of the new variants of concern. Only 0.08% of the population from six countries received at least one dose of the COVID-19 vaccine. It is critical to not only learn from the past 12 months to improve the effectiveness of the current response but also to start preparing the health systems for subsequent waves of the current pandemic and future pandemics.