Objective: Major system change (MSC) has multiple, sometimes conflicting, goals and involves implementing change across a number of organizations. This study sought to develop new understanding of how the role that networks can play in implementing MSC, using the case of centralization of specialist cancer surgery in London, UK. Methods: The study was based on a framework drawn from literature on networks and MSC. We analysed 100 documents, conducted 134 h of observations during relevant meetings and 81 interviews with stakeholders involved in the centralization. We analysed the data using thematic analysis. Results: MSC in specialist cancer services was a contested process, which required constancy in network leadership over several years, and its horizontal and vertical distribution across the network. A core central team composed of network leaders, managers and clinical/manager hybrid roles was tasked with implementing the changes. This team developed different forms of engagement with provider organizations and other stakeholders. Some actors across the network, including clinicians and patients, questioned the rationale for the changes, the clinical evidence used to support the case for change, and the ways in which the changes were implemented. Conclusions: Our study provides new understanding of MSC by discussing the strategies used by a provider network to facilitate complex changes in a health care context in the absence of a system-wide authority