BACKGROUND: Chronic diseases contribute to high rates of disability and mortality. Patient engagement in chronic disease self-management is an essential component of chronic disease models of health care. Wearables provide patient-centered health data in real time, which can help inform self-management decision-making. Despite the perceived benefits of wearables in improving chronic disease self-management, their influence on health care outcomes remains poorly understood. OBJECTIVE: This review aimed to examine the influence of wearables on health care outcomes in individuals with chronic diseases through a systematic review of the literature. METHODS: A narrative systematic review was conducted by searching 6 databases for randomized and observational studies published between January 1, 2016, and July 1, 2021, that included the use of a wearable intervention in a chronic disease group to assess its impact on a predefined outcome measure. These outcomes were defined as any influence on the patient or clinician experience, cost-effectiveness, or health care outcomes as a result of the wearable intervention. Data from the included studies were extracted based on 6 key themes, which formed the basis for a narrative qualitative synthesis. All outcomes were mapped against each component of the Quadruple Aim of health care. The guidelines of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement were followed in this study. RESULTS: A total of 30 articles were included; studies reported 2446 participants (mean age: range 10.1-74.4 years), and the influence of 14 types of wearables on 18 chronic diseases was presented. The most studied chronic diseases were type 2 diabetes (4/30, 13%), Parkinson disease (3/30, 10%), and chronic lower back pain (3/30, 10%). The results were mixed when assessing the impact on a predefined primary outcome, with 50% (15/30) of studies finding a positive influence on the studied outcome and 50% (15/30) demonstrating a nil effect. There was a positive effect of 3D virtual reality systems on chronic pain in 7% (2/30) of studies that evaluated 2 distinct chronic pain syndromes. Mixed results were observed in influencing exercise capacity; weight; and biomarkers of disease, such as hemoglobin A, in diabetes. In total, 155 outcomes were studied. Most (139/155, 89.7%) addressed the health care outcomes component. This included pain (11/155, 7.5%), quality of life (7/155, 4.8%), and physical function (5/155, 3.4%). Approximately 7.7% (12/155) of outcome measures represented the patient experience component, with 1.3% (2/155) addressing the clinician experience and cost. CONCLUSIONS: Given their popularity and capability, wearables may play an integral role in chronic disease management. However, further research is required to generate a strong evidence base for safe and effective implementation. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42021244562; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=244562.