OBJECTIVES: To explore the opportunities and challenges within the health system to facilitate the achievement of universal health coverage (UHC) for people with stroke (PWS) in South Africa (SA). SETTING: SA. DESIGN: Scoping review. SEARCH METHODS: We conducted a scoping review of opportunities and challenges to achieve UHC for PWS in SA. Global and Africa-specific databases and grey literature were searched in July 2020. We included studies of all designs that described the healthcare system for PWS. Two frameworks, the Health Systems Dynamics Framework and WHO Framework, were used to map data on governance and regulation, resources, service delivery, context, reorientation of care and community engagement. A narrative approach was used to synthesise results. RESULTS: Fifty-nine articles were included in the review. Over half (n=31, 52.5%) were conducted in Western Cape province and most (n=41, 69.4%) were conducted in urban areas. Studies evaluated a diverse range of health system categories and various outcomes. The most common reported component was service delivery (n=46, 77.9%), and only four studies (6.7%) evaluated governance and regulation. Service delivery factors for stroke care were frequently reported as poor and compounded by context-related limiting factors. Governance and regulations for stroke care in terms of government support, investment in policy, treatment guidelines, resource distribution and commitment to evidence-based solutions were limited. Promising supporting factors included adequately equipped and staffed urban tertiary facilities, the emergence of Stroke units, prompt assessment by health professionals, positive staff attitudes and care, two clinical care guidelines and educational and information resources being available. CONCLUSION: This review fills a gap in the literature by providing the range of opportunities and challenges to achieve health for all PWS in SA. It highlights some health system areas that show encouraging trends to improve service delivery including comprehensiveness, quality and perceptions of care.