Sickle cell disease is caused by an abnormality of the β-globin gene and is characterised by sickling of the red blood cells. Globally, sub-Saharan African countries share the highest burden of the disease. This study aimed at critically reviewing studies focusing on challenges of sickle cell anaemia in sub-Saharan Africa. A literature search was carried out in five major databases. Articles that met the inclusion criteria were included in the bibliometric review and critical analysis. A majority of the studies were undertaken in the West African region (85.5%), followed by Central Africa (9.1%). Very few studies had been undertaken in East Africa (3.6%), whilst the Southern African region had the fewest studies (1.8%). Distribution in relation to country revealed that three quarters of the studies were carried out in Nigeria (74.5%), followed by the Democratic Republic of the Congo (9.1%). According to healthcare settings, a strong majority of the studies were undertaken in tertiary health care facilities (92.7%). Major themes that emerged from the review include interventions, cost of treatment, and knowledge about sickle cell disease. Public health awareness and promotion as well as improving the quality of sickle cell centers for prompt management of patients with sickle cell disorder was identified as a critical strategy towards reducing the burden of the disease in sub-Saharan Africa. To achieve this, governments in countries located in this region need to adopt a proactive strategy in addressing gaps that have been identified in this study, as well as instituting other relevant measures, such as continuous media engagement and public health interventions relating to genetic counselling. Reforms in other areas that can help reduce the disease burden, include training of practitioners and equipping sickle cell disease treatment centers according to World Health Organization specifications.