There is increasing attention on evidencing research impact and applying a systems thinking perspective in public health. However, there is limited understanding of the extent to which and how public health research that applies a systems thinking perspective contributes to changes in system behaviour and improved population health outcomes. This paper addresses the theoretical limitations of research impact, theory-based evaluation and systems thinking, by drawing on their respective literature to develop an initial, middle-range Theory of Systems Change, focused on the contribution of public health research that takes a systems perspective on population health outcomes. The Theory of Systems Change was developed through four phases: (1) Preliminary activities, (2) Theory development, (3) Scripting into images, and (4) Examining against Merton's criteria. The primary propositions are: that well-functioning systems create the conditions for improved population health outcomes; the inter-related properties of, and practices within, well-functioning systems include adaptation, alignment, collaboration and evidence-driven action and learning; and public health research contributes to population health outcomes by embedding capacity in the system. The Theory of Systems Change can guide researchers in developing project-specific theories of change and creates the theoretical architecture for the accumulation of learning. The Theory of Systems Change is necessarily incomplete and an initial attempt to develop a theory to be scrutinized and tested. Ultimately, it seeks to advance theory and provide evidence-based guidance to maximize the contribution of research. We provide examples of how we have applied the Theory of Systems Change to Pathways in Place.