This article proposes a processual–relational perspective on region-making and its effects in world politics. It revisits the concepts of regionalism and regionalisation to unearth the relational mechanisms underlying these archetypical pathways of regional emergence. Regionalism refers to the bounding of regions – the definition of its inside and outside, and of which actors fall on either side. Regionalisation denotes the binding of regions, the amalgamations of relations around a shared territoriality. I argue that regions affect world politics in their making through the boundaries raised and relations produced in the process. I then mobilise network theory and analysis to propose a framework for studying the making and makings of regions. Regions’ binding and bounding are rooted in brokerage dynamics that sustain clusters of relations denser inside a regional boundary, rather than outside, and allow some actors to control interactions across that boundary. I illustrate this framework with a case study on the emergence of the Amazon as a region in world politics. I analyse interaction networks in UN-level environmental negotiations involving the ecosystem. The analysis shows how the making of the Amazon has been tied to preserving the position of Amazonian states as the main brokers, speaking for and acting on behalf of the region.