IntroductionSystems science methodologies have been used in attempts to address the complex and dynamic causes of childhood obesity with varied results. This paper presents a protocol for the Reflexive Evidence and Systems interventions to Prevention Obesity and Non-communicable Disease (RESPOND) trial. RESPOND represents a significant advance on previous approaches by identifying and operationalising a clear systems methodology and building skills and knowledge in the design and implementation of this approach among community stakeholders.Methods and analysisRESPOND is a 4-year cluster-randomised stepped-wedge trial in 10 local government areas in Victoria, Australia. The intervention comprises four stages: catalyse and set up, monitoring, community engagement and implementation. The trial will be evaluated for individuals, community settings and context, cost-effectiveness, and systems and implementation processes. Individual-level data including weight status, diet and activity behaviours will be collected every 2 years from school children in grades 2, 4 and 6 using an opt-out consent process. Community-level data will include knowledge and engagement, collaboration networks, economic costs and shifts in mental models aligned with systems training. Baseline prevalence data were collected between March and June 2019 among >3700 children from 91 primary schools.Ethics and disseminationEthics approval: Deakin University Human Research Ethics Committee (HREC 2018-381) or Deakin University’s Faculty of Health Ethics Advisory Committee (HEAG-H_2019-1; HEAG-H 37_2019; HEAG-H 173_2018; HEAG-H 12_2019); Victorian Government Department of Education and Training (2019_003943); Catholic Archdiocese of Melbourne (Catholic Education Melbourne, 2019-0872) and Diocese of Sandhurst (24 May 2019). The results of RESPOND, including primary and secondary outcomes, and emerging studies developed throughout the intervention, will be published in the academic literature, presented at national and international conferences, community newsletters, newspapers, infographics and relevant social media.Trial registration numberACTRN12618001986268p.