Chronic diseases are the major cause of death in Australia and the biggest contributor to premature death and disability. Although prevention of chronic disease can be effective and cost-effective, it has proven difficult to systematically implement interventions that target important lifestyle-related risk factors for chronic disease such as poor nutrition, physical inactivity and harmful alcohol use. Prevention efforts targeting these lifestyle-related risk factors have had mixed success due to issues around designing and implementing effective interventions that address the complexity of risk factors, and incorporating evidence and implementing interventions at a scale, duration, intensity and quality required to achieve population effects. There is increasing recognition that multilevel, multisector approaches are required for the effective and sustained prevention of complex chronic disease. The Australian Prevention Partnership Centre, one of two National Health and Medical Research Council Partnership Centres established in 2013, is researching and developing systems perspectives to prevent lifestyle-related chronic disease in Australia. The Centre's collaborative approach is providing opportunities for researchers to work with policy makers and practitioners to develop research questions, conduct research, and analyse, interpret and disseminate the findings. As such, it is the model of interaction that is being tested as much as the specific projects. With its funding partners, the Centre has developed plans for more than 30 projects. It has also established four capacity units that will improve the gathering, sharing and use of evidence to build a prevention system in Australia. The Centre is exploring new ways to advance prevention by bringing together researchers, policy makers and practitioners to determine the information and actions needed for an effective prevention system for Australia.