Abstract The application of data science methodologies to large-scale diverse and complex biomedical datasets for novel discoveries requires access to data, tools, workflows and computing infrastructure, along with training and support. With many of these lacking in Africa, including the skills for execution, there is a need to develop new infrastructure that takes into account the African context and addresses barriers present in low and middle income countries. We will develop an Open Data Science Gateway for the DS-I Africa consortium that includes the eLwazi platform and associated training, supporting tools and resources. eLwazi, symbolizing “knowledge”, will be a modular, scalable platform based on the Data Biosphere concept, that enables the application of data science tools to drive novel discoveries for health. From eLwazi workspaces, novice and advanced users will be able to: 1) search for data in a data repository and catalogue; 2) retrieve relevant datasets stored locally or at federated sites; 3) search and retrieve relevant tools and workflows; 4) execute their analyses on a choice of computing environment; and 5) visualize and share their results. Users will be an integral part of the development process, providing input on their needs and feedback, and will be supported through a helpdesk, user groups and a comprehensive data science training program. We will develop a transparent cost model and build African skills and infrastructure to ensure long term sustainability of the platform. The Open Data Science Gateway will facilitate open, collaborative research that strives to develop novel health applications in Africa and beyond. This African led initiative aligns with the vision and requirements of the emerging African Open Science Platform. An active outreach program will extend the reach of eLwazi to other cohorts, datasets and consortia and promote partnerships in academia and industry. Leveraging H3ABioNet’s expertise and capacity developed since 2012 together with international expertise from the leaders in the field, and using existing frameworks and standards will ensure a successful platform is implemented timeously and is interoperable with Common Fund programs and other international initiatives to ensure global applicability.