Within the field of chronic disease prevention, research efforts have moved to better understand, describe, and address the complex drivers of various health conditions. Change-making is prominent in this paper, and systems thinking and systems change are prioritised as core elements of prevention research. We report how the process of developing a theory of systems change can assist prevention research to progress from understanding systems, towards impactful action within those systems. Based on Foster-Fishman and Watsonâ€™s ABLe change framework, a Prevention Systems Change Framework (PSCF) was adapted and applied to an Australian case study of the drivers of healthy and equitable eating as a structured reflective practice. The PSCF comprises four components: building a systemic lens on prevention, holding a continual implementation focus, integrating the systemic lens and implementation focus, and developing a theory of change. Application of the framework as part of a systemic evaluation process enabled a detailed and critical assessment of the healthy and equitable eating project goals and culminated in the development of a theory of prevention systems change specific to that project, to guide future research and action. Arguably, if prevention research is to support improved health outcomes, it must be more explicitly linked to creating systems change.