The coronavirus 2019 (COVID-19) pandemic has impacted Sub-Saharan African health systems, caused economic downturns, and put governments under intense pressure to deliver hope to their citizens. However, the unknowns of the SARS-CoV-2 virus are a concern for many experts. This paper discusses lessons from Sub-Saharan African countries and lessons from other countries regarding pandemic management. The paper identifies five lessons from Africa’s management of the COVID-19 pandemic: mutation of the SARS-CoV-2 virus, COVID-19 vaccines waning over time, the threat of vaccine hesitancy in Africa, reliance on vertical health systems and lack of knowledge on political determinants of health by African leaders. Finally, drawing lessons from the current COVID-19 pandemic response from Sub-Saharan African governments and some countries could help them improve their response to the ongoing COVID-19 pandemic.