The successful implementation of comprehensive sexuality education (CSE) programmes in schools depends on the development and implementation of strong policy in support of CSE. This paper offers a comparative analysis of the policy environment governing school-based CSE in four low- and middle-income countries at different stages of programme implementation: Ghana, Peru, Kenya and Guatemala. Based on an analysis of current policy and legal frameworks, key informant interviews and recent regional reviews, the analysis focuses on seven policy-related levers that contribute to successful school-based sexuality education programmes. The levers cover policy development trends; current policy and legal frameworks for sexuality education; international commitments affecting CSE policies; the various actors involved in shaping CSE; and the partnerships and coalitions of actors that influence CSE policy. Our analysis shows that all four countries benefit from a policy environment that, if properly leveraged, could lead to a stronger implementation of CSE in schools. However, each faces several key challenges that must be addressed to ensure the health and wellbeing of their young people. Latin American and African countries show notable differences in the development and evolution of their CSE policy environments, providing valuable insights for programme development and implementation.