Despite progress on the Millennium and Sustainable Development Goals, significant public health challenges remain to address communicable and non-communicable diseases and health inequities. The Healthier Societies for Healthy Populations initiative convened by WHO’s Alliance for Health Policy and Systems Research; the Government of Sweden; and the Wellcome Trust aims to address these complex challenges. One starting point is to build understanding of the characteristics of successful government-led interventions to support healthier populations. To this end, this project explored five purposefully sampled, successful public health initiatives: front-of-package warnings on food labels containing high sugar, sodium or saturated fat (Chile); healthy food initiatives (trans fats, calorie labelling, cap on beverage size; New York); the alcohol sales and transport ban during COVID-19 (South Africa); the Vision Zero road safety initiative (Sweden) and establishment of the Thai Health Promotion Foundation. For each initiative a qualitative, semistructured one-on-one interview with a key leader was conducted, supplemented by a rapid literature scan with input from an information specialist. Thematic analysis of the five interviews and 169 relevant studies across the five examples identified facilitators of success including political leadership, public education, multifaceted approaches, stable funding and planning for opposition. Barriers included industry opposition, the complex nature of public health challenges and poor interagency and multisector co-ordination. Further examples building on this global portfolio will deepen understanding of success factors or failures over time in this critical area.