Abstract Generating actionable knowledge to meet current sustainability challenges requires unprecedented collaboration across scales, geographies, cultures and knowledges. Intergovernmental programmes and place‐based knowledge–action networks have much potential to mobilize sustainability transformation. Although many research fields have benefited from research networks and comparative sites, the potential of site‐based research networks for generating knowledge at the people–nature interface has yet to be fully explored. This article presents the World Network of biosphere reserves (WNBR) of UNESCO's Man and Biosphere Programme, intentionally established for generating actionable knowledge through comparative sites envisioned as learning spaces for sustainable development. Drawing on experiences over five decades, and we offer six categories of insights. Our intent is to share the story of this network widely, distil the learnings from the network to enhance its potential to support both knowledge co‐production and collaborative action for sustainability and inform wider efforts to establish place‐based sustainability networks aimed at improving human–environment relations through knowledge and action. The WNBR has generated insights on the challenges of creating and supporting an international and inter‐governmental sustainability network to generate and mobilize place‐based interdisciplinary knowledge in the long term. Despite the challenges, site‐ and place‐based research facilitated by this network has been fundamental in creating space for sustainability science, knowledge co‐production and transdisciplinary research at the human–nature interface. We share insights on pathways to the implementation of global sustainability agendas through local networks, and the role of research in supporting learning and experimentation in local sites as they work to adapt global sustainability goals. Research in the WNBR has generated deeper understanding on social–ecological complexity and resilience in place‐based sustainability initiatives, and how collaborative platforms might facilitate collective action across landscapes. The network continues to offer a fundamental learning space on operationalizing pluralistic approaches to biodiversity conservation, for example, through its focus on biocultural diversity, offering a key opportunity for the implementation of the post‐2020 Global Biodiversity Framework. We conclude by arguing that WNBR, and similar place‐based knowledge–action networks, can support interdisciplinary and transdisciplinary research related to human–nature relationships and provide opportunities for comparative research that may yield more explanatory power than individual case studies. Read the free Plain Language Summary for this article on the Journal blog.