Poor self-care behaviors can lead to an increase in the risk of adverse health outcomes among patients with heart failure. Although a number of studies have investigated the effectiveness of nurse-led self-care education, the evidence regarding the effects of nurse-led intervention in heart failure remains uncertain. This study aimed to evaluate evidence on the effectiveness of nurse-led heart failure self-care education on health outcomes in patients with heart failure. To identify studies testing nurse-led education designed to improve self-care among heart failure patients, comprehensive search methods were used between January 2000 and October 2019 to systematically search six electronic databases: PubMed, CINAHL, Embase, Cochrane library, Web of Science, and SCOPUS. All the eligible study data elements were independently assessed and analyzed using random-effects meta-analysis methods. Of 612 studies, eight articles were eligible for this study. Nurse-led heart failure self-care education significantly reduced the risk of all-cause readmission (risk ratio (RR) = 0.75, 95% confidence interval (CI) = 0.66–0.85), heart failure specific readmission (RR = 0.60, 95% CI = 0.42–0.85), and all-cause mortality or readmission (RR = 0.71, 95% CI = 0.61–0.82). However, nurse-led heart failure self-care education was not associated with improvements in the quality of life and heart failure knowledge. Studies on the effectiveness of nurse-led heart failure self-care education mostly report only the positive effects on patients’ health outcomes, whereas evidence of the effectiveness of the nurse-led approach is still limited. Therefore, high quality randomized controlled trials with detailed and explicit descriptions on the components of the interventions are needed.