Background: With rising time constraints, health care professionals increasingly depend on technology to provide health advice and teach patients how to manage chronic disease. The effectiveness of video-based tools in improving knowledge, health behaviors, disease severity, and health care use for patients with major chronic illnesses is not well understood. Objective: The aim of this study was to assess the current literature regarding the efficacy of video-based educational tools for patients in improving process and outcome measures across several chronic illnesses. Methods: A systematic review was conducted using CINAHL and PubMed with predefined search terms. The search included studies published through October 2021. The eligible studies were intervention studies of video-based self-management patient education for an adult patient population with the following chronic health conditions: asthma, chronic kidney disease, chronic obstructive pulmonary disease, chronic pain syndromes, diabetes, heart failure, HIV infection, hypertension, inflammatory bowel disease, and rheumatologic disorders. The eligible papers underwent full extraction of study characteristics, study design, sample demographics, and results. Bias was assessed with the Cochrane risk-of-bias tools. Summary statistics were synthesized in Stata SE (StataCorp LLC). Data reporting was conducted per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. Results: Of the 112 studies fully extracted, 59 (52.7%) were deemed eligible for inclusion in this review. The majority of the included papers were superiority randomized controlled trials (RCTs; 39/59, 66%), with fewer pre-post studies (13/59, 22%) and noninferiority RCTs (7/59, 12%). The most represented conditions of interest were obstructive lung disease (18/59, 31%), diabetes (11/59, 19%), and heart failure (9/59, 15%). The plurality (28/59, 47%) of video-based interventions only occurred once and occurred alongside adjunct interventions that included printed materials, in-person counseling, and interactive modules. The most frequently studied outcomes were disease severity, health behavior, and patient knowledge. Video-based tools were the most effective in improving patient knowledge (30/40, 75%). Approximately half reported health behavior (21/38, 56%) and patient self-efficacy (12/23, 52%) outcomes were improved by video-based tools, and a minority of health care use (11/28, 39%) and disease severity (23/69, 33%) outcomes were improved by video-based tools. In total, 48% (22/46) of the superiority and noninferiority RCTs and 54% (7/13) of the pre-post trials had moderate or high risk of bias. Conclusions: There is robust evidence that video-based tools can improve patient knowledge across several chronic illnesses. These tools less consistently improve disease severity and health care use outcomes. Additional study is needed to identify features that maximize the efficacy of video-based interventions for patients across the spectrum of digital competencies to ensure optimized and equitable patient education and outcomes.