SummaryMotivationAlthough the field of evidence‐informed policy‐making has grown significantly in the last 20 years, little is written about how it manifests within government policy, and whether it makes a meaningful difference to development outcomes. This article seeks to fill that gap.PurposeThrough reflection and analysis of shifts in the wider evidence ecosystem, and developments in South Africa specifically, the article describes how in South Africa the political and policy spheres come together with changes in production and use of evidence to increase the potential to improve the lives of millions of people.Methods and approachThis article is based on structured reflection and analysis of 20 years of contributions to the evidence ecosystem in low‐, lower‐middle, and upper‐middle income countries (L&MICs), in particular in Africa. It includes analysis of documentation of initiatives, policies, and practices relating to the production and use of evidence, with a focus on South Africa.FindingsThere are clear shifts within evidence‐informed decision‐making (EIDM) systems over time in the production of evidence and in the implementation of evidence approaches. The varied experiences documented in South Africa and across L&MICs highlight valuable lessons for others. In South Africa the policies underpinning evidence use, and the political context in which evidence‐informed decision‐making takes place, combine to contribute to increasing use of evidence in the country. Reflecting on the system developments across Africa and further afield reveals how one country's system is both influenced by these wider contexts and has potential to influence the wider system with clear policy implications.Policy implicationsRoutine use of evidence in decision‐making requires new practices to become standard across not only policy systems, but also evidence systems. Changes are needed across a range of actors, organizations, and institutions. There are lessons to be learnt from varied experiences including those in L&MICs, to inform advances towards the institutionalization of evidence use in policy. This case study highlights the importance of synergistic developments in both evidence production and use, of genuine partnerships at all levels, and of the policies and frameworks that underpin change.