The first case of coronavirus disease of 2019 (COVID-19) in South Africa (SA) was first reported at the beginning of March 2022, and then further spread from Gauteng, Western Cape, and KwaZulu Natal to the rest of the provinces. It is caused by severe acute respiratory syndrome coronavirus 2. In SA, COVID-19 is less prevalent in children less than 18 years. Only a few studies describe the epidemiology, risk factors, and clinical manifestation of COVID-19 among children in SA in comparison to other countries including China, North America, and Europe. South African children are affected by conditions including poverty, tuberculosis, and human immunodeficiency virus which predispose them to COVID-19. Overcrowding and limited healthcare facilities and resources also complicated the diagnosis and clinical and pharmacological management of COVID-19 in SA. The current review discusses the prevalence, risk factors, and management of COVID-19 in South African children in comparison to other continents in the world.