The increasing adoption of Artificial Intelligence (AI) necessitates effective regulation, especially in Africa, owing to its varied socioeconomic conditions. This study examines AI governance in Africa in terms of three dimensions a) identifies regulatory challenges, infrastructure, and Cultural challenges, b) strategies for responsible AI, c) proposes an approach for responsible AI, and d) recommendations for fostering responsible AI development by African Economies. A review of academic literature, sector reports, and case studies was conducted. A comparative analysis was conducted to identify the best AI regulatory framework. Despite varying AI adoption levels, common infrastructure, and cultural challenges in African countries, certain regions have shown promising AI applications and regulatory progress. This study emphasizes responsible AI and proposes a flexible approach to its regulations in Africa. It integrates contextual, anticipatory, principle-based, experimental, data-driven, joint, and cooperative regulations to adapt to the continent’s unique challenges and opportunities. AI can benefit African countries when guided by comprehensive, versatile, and inclusive regulations. Industries must collaborate and adopt global best practices to unlock their potential.