Background: The COVID-19 pandemic has continued to spread throughout the globe and in all African countries with major public health and economic impacts. Methods: We have conducted a detailed synthesis of intra-action review (IAR) reports from 18 countries in the World Health Organization (WHO) African Region, which were available as of March 2021. We conducted a thematic analysis across ten preparedness and response domains, namely, governance, leadership and coordination; planning and monitoring; risk communication and community engagement; surveillance, rapid response and case investigation; infection prevention and control; case management; screening and monitoring at points of entry; national laboratory system; logistics and supply chain management; and maintaining essential health services during the COVID-19 pandemic. Findings: The COVID-19 pandemic response in African countries has relied on many existing response systems such as laboratory systems, surveillance systems for previous outbreaks of highly infectious diseases, and a logistics management information system. These best practices were backed by strong political will. The key challenges included low public confidence in governments, inadequate adherence to infection prevention and control measures, shortages of personal protective equipment, inadequate laboratory capacity, inadequate contact tracing, poor supply chain and logistics management systems, and lack of training of key personnel at national and sub-national levels. Interpretation: These findings suggest that African countries’ response to the COVID-19 pandemic was prompt and may have contributed to the lower cases and deaths in the region compared to countries in other regions. The IARs demonstrate that many technical areas still require immediate improvement to guide decisions in subsequent waves or future outbreaks. Funding Information: World Health Organization Regional Office for Africa. Declaration of Interests: We declare no competing interests.