Abstract The School Health Research Network (SHRN) was launched in Wales in 2013 as a strategic partnership between Cardiff University, Welsh Government, Public Health Wales (part of the National Health Service) and Cancer Research UK (a research-focused charity). SHRN is led by a multidisciplinary team in the Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer) at Cardiff University. SHRN aims to: 1) provide health and well-being data from a biennial survey for national, regional and local stakeholders, including schools; 2) co-produce school-based health improvement research for Wales; and 3) build capacity for evidence-informed public health policy and practice. Building on and integrating with HBSC infrastructure, a transdisciplinary complex adaptive systems (T-CAS) approach has been employed to develop SHRN, for a national culture of prevention for school health improvement. The T-CAS approach focuses on key stages and activities within a continuous network cycle to facilitate systems level change. The five key stages involve establishing transdisciplinary strategic partnerships, resource investment and linkage, network development, coproduction activities and reciprocal outputs. SHRN has successfully established new cross-sector stakeholder partnerships at multiple levels, and embedded network activity within national and local policy. It has established a programme of school engagement activities to secure membership of 212 (100%) secondary schools in Wales and building on HBSC systems and structures has developed a national data infrastructure with the biennial collection of student and school-level health and wellbeing data. SHRN has co-produced scientific evidence and established a new data-led planning system (e.g. 56 research studies co-produced). It has also secured sustainability funding from health and education, while developing research capacity to generate evidence and support professional practice.