Substantial investment in digital solutions for improved health services has occurred in recent years in Africa. Digital Health provides for proven, beneficial applications in many different areas of health systems. It supports the transformation of healthcare delivery, and its potential is seemingly boundless. However, the deployed systems are in silos, and interoperability and integration are largely missing. There is no timely information for easy and quick decision making; there is no ability to track service levels across the whole health sector. What is missing is an integrated information system across all healthcare facilities nationwide. Such a Digital Health Ecosystem, the holistic application of information and communications technologies, services and applications, will support health systems and improve healthcare delivery, coordination and integration across providers. Based on global experience in resource-constraint contexts, core steps necessary to develop and implement such an ecosystem are explored, and four fundamental building blocks and their elements are developed. The results presented are succinctly integrated into six statements on lessons learned and recommendations.