Clinical trial (CT) safety surveillance is critical to protecting participants and ensuring reliable evidence on the safety and efficacy of new medical products. This is especially relevant in Africa, where CT activity remains limited, regulatory maturity varies, and drug safety surveillance systems are under-resourced despite considerable demographic advantages and genetic and cultural diversity. To assess the current state of CT safety surveillance in Africa, a landscape analysis of the systems for clinical trial safety data reporting, collation, and analysis was conducted. Despite challenges, opportunities exist to strengthen CT safety surveillance through digitization of reporting systems, harmonization of serious adverse event forms, regional collaboration, and capacity building for strengthening the ecosystem. The results of this landscape analysis provide a roadmap for building a coordinated model for pre-licensure safety monitoring across the continent.