Description: Introduction The burden of chronic disease is a global phenomenon, particularly among people aged 65 years and older. More than half of older adults have more than one chronic disease and their care is not optimal. Chronic disease management (CDM) tools have the potential to meet this challenge but they are primarily focused on a single disease, which fails to address the growing number of seniors with multiple chronic conditions. Methods and analysis We will conduct a systematic review alongside a realist review to identify effective CDM tools that integrate one or more high-burden chronic diseases affecting older adults and to better understand for whom, under what circumstances, how and why they produce their outcomes. We will search MEDLINE, EMBASE, CINAHL, AgeLine and the Cochrane Library for experimental, quasi-experimental, observational and qualitative studies in any language investigating CDM tools that facilitate optimal disease management in one or more high-burden chronic diseases affecting adults aged ≥65 years. Study selection will involve calibration of reviewers to ensure reliability of screening and duplicate assessment of articles. Data abstraction and risk of bias assessment will also be performed independently. Analysis will include descriptive summaries of study and appraisal characteristics, effectiveness of each CDM tool (meta-analysis if appropriate); and a realist programme theory will be developed and refined to explain the outcome patterns within the included studies. Ethics and dissemination Ethics approval is not required for this study. We anticipate that our findings, pertaining to gaps in care across high-burden chronic diseases affecting seniors and highlighting specific areas that may require more research, will be of interest to a wide range of knowledge users and stakeholders. We will publish and present our findings widely, and also plan more active dissemination strategies such as workshops with our key stakeholders. Trial registration number Our protocol is registered with PROSPERO (registration number CRD42014014489).