The future of societies and ecosystems worldwide depends on the adaptive management of complex interactions between biodiversity, climate and human activities and their impacts on human, animal and environmental health. We focus on agricultural activities which have a direct impact on food systems and living conditions, particularly in developing tropical or subtropical countries, due to high socio- economic dependency on agriculture, often deficient public health infrastructures, and high vulnerabilities to climate change and biodiversity erosion. The scope of One Health (OH) has been gradually broadened, from an initial focus on public health and zoonotic diseases affecting humans, domestic and wild animals, to include plants and ecosystem health. This expansion was endorsed by the United Nations Quadripartite Alliance of United Nations organizations on health1 and the associated OH Joint Plan of Action2. However, the operational application of this updated OH approach to address health and agricultural issues in tropical low-income countries is both promising and concerning. We analysed four recent and ongoing interdisciplinary action-research projects addressing health issues in various agro-ecosystems in Africa and SE Asia: i) AfriCam project3 aims at strengthening local collective capacities for action to prevent and manage the emergence of health risks. In a context of land transformation by agriculture in Cameroon, the approach adopted the concept of integrated health4 to generate and share common knowledge on agrobiodiversity to mobilise collective action and public policies to prevent zoonoses; ii) MozARH5 project investigated the evolution of the relations between humans and rodents in areas adjacent to the Limpopo National Park in Mozambique. It illustrates how a changing socioecological landscape can create new viral routes, including in areas apparently little affected by anthropogenic transformation6, questioning the idea of “natural” equilibrium; iii