Background: The coronavirus disease 2019 (COVID-19) is a public health problem that has caused harm to the mental health of healthcare workers. In Africa, the COVID-19 pandemic has led healthcare workers to experience mental health disorders such as anxiety, depression, stress, insomnia and burnout. This study aimed to review published studies on the effect of COVID-19 on the mental health of healthcare workers, associated factors and coping strategies that have been employed in Africa. Methods: This was a systematic review that was conducted through searching databases including; PubMed/Medline and Google Scholar. The study included published literature from January 2020 to May 2022 that met the inclusion criteria. The selection of articles was conducted following the 2020 PRISMA guidelines. Results: A total of 39 articles were retrieved, of which only 18 met the inclusion criteria and were used in this study. Our review revealed that healthcare workers experienced mental health disorders such as anxiety, depression, insomnia, stress and burnout that were associated with the COVID-19 pandemic. Coping strategies such as religious practices, support from family members and colleagues and avoiding listening to social media about COVID-19 were used to minimize mental health problems. Conclusion: The COVID-19 pandemic has caused increased mental health disorders among healthcare workers in Africa. Identification of factors associated with mental health problems is cardinal in developing coping mechanisms against the psychological impact of COVID-19. Therefore, there is a need for governments to develop and implement strategies for protecting the mental health of healthcare workers during crises such as the COVID-19 pandemic.