Sickle cell disease (SCD) is a genetic blood disorder in high prevalence in sub-Saharan Africa (SSA) that leads to high morbidity and early mortality. Newborn screening (NBS) with evidence-based interventions saves lives of individuals with SCD. SSA accounts for 75% of the global prevalence of SCD, but it has not been able to implement universal NBS for SCD. This article examines policy framework for NBS in SSA; the methods, processes, barriers, and enablers of NBS; and enrollment in comprehensive care to make available the evidence-based interventions that caregivers need to access in order to save the lives of babies with SCD.