Background <p>Sickle cell anemia is an inherited hematological disease with significant morbidity and mortality, particularly in resource-limited settings. Stroke is preventable through transcranial Doppler ultrasonography screening, identifying high-risk children for preventive hydroxyurea treatment.</p> Objectives <p>Describe how public health leaders can mitigate stroke risk in sub-Saharan Africa through ultrasonography training and supervision. Secondary objectives included describing operational and systemic factors influencing training and implementation in these settings; exploring leadership skills to improve clinical care; assessing technology and knowledge transfer as drivers of stroke screening and prevention; and providing recommendations for stroke screening in the context of safe, effective, and culturally-appropriate care, including disease-modifying hydroxyurea therapy.</p> Methods <p>We used a qualitative design with 17 semi-structured interviews of examiners and stakeholders from six countries across sub-Saharan Africa. Interviews were coded and analyzed using Grounded Theory to identify effective training and program strategies and develop a capacity-building model supporting stroke prevention.</p> Results <p>In-person training with African examiners was preferred over web-based platforms, and ongoing training, supervision, and support through United States-African collaborations increased skill development. Participants described the major clinical and socioeconomic impacts of sickle cell anemia on children, families and communities and emphasized the role of hydroxyurea to prevent complications and decrease health system burden.</p> Conclusions <p>A multifaceted approach to sickle cell capacity building with education, policy development, training, and hydroxyurea offers a holistic approach that leverages geographical partnerships and builds on existing resources in sub-Saharan Africa to provide safe, effective, and sustainable care that improves outcomes for children worldwide.</p>