The United Nations Environment Programme (UN Environment) launched at the end of 2016 a decade-long (2016–2025) flagship programme on Climate, Ecosystems and Livelihoods (CEL), with the aim to assist developing countries in delivering the Sustainable Development Goals (SDGs) and climate targets while protecting their ecosystems and improving the livelihoods of their people. The CEL programme is a major initiative supported by China and other developing countries to promote long-term South-South cooperation, led by the United Nations Environment Programme International Ecosystem Management Partnership (UNEP-IEMP). This article presents the conceptual framework and implementation strategy of the CEL programme, which were proposed through consultations between UN Environment, Chinese and international experts. Within the conceptual framework, the CEL programme will 1) focus its work on the nexus of climate change, ecosystem services and sustainable livelihoods as the primary priority; 2) encourage cross-sectoral and multi-stakeholder cooperation, enhance interdisciplinary research, and strive for breakthroughs that cross disciplinary boundaries; 3) provide four types of services and products—monitoring and assessment, capacity building, technology demonstration, and science for policy through mainly South-South cooperation; and 4) have far-reaching impacts on delivering SDGs and climate targets in vulnerable developing countries. The CEL programme is going to be implemented in a strategic way through a set of related projects and initiatives. More particularly, it will 1) focus on fragile ecosystems like drylands, mountains, river basins and coastal zones in Asia, Africa and other key regions along the Belt and Road, in the early stage and expand to include some other regions at a later stage; 2) take a three-phase approach, including Phase I, Kick -off (2016–2018), Phase II, Development (2019–2021), and Phase III, Scaling-up (2022–2025); and 3) draw on the globally relevant knowledge, expertise and other resources of a substantial network of partners. So far, UNEP-IEMP has developed more than twenty projects and initiatives in the regions along the Belt and Road, especially in Africa and the Greater Mekong Subregion, which lay a solid foundation for the implementation of CEL programme in its first phase.