Background Chronic disease is responsible for 80% of the burden of disease in Australia. The Australian Government Medicare Benefits Schedule (MBS) provides incentives through specific Medicare items to optimise chronic disease management (CDM), yet little is known about factors that influence their uptake. Methods Exploratory qualitative research was used, which incorporated focus groups and interviews with 26 staff from nine general practices in southeast Queensland, together with review of practice-specific data on CDM income. Content analysis of qualitative data was undertaken to identify barriers, enablers and service models associated with MBS CDM item uptake. Triangulation of methods and data sources facilitated confirmation of findings. Results Time pressures and unreliable MBS information were common barriers to uptake for general practitioners. Employing a nurse, team-based approaches, recall systems and using only selected MBS CDM item numbers were associated with best uptake. Conclusion Improved systems within general practice and Medicare may increase the uptake of MBS CDM item numbers.