The objectives of this systematic review were to estimate the prevalence of depression and to identify the relationship between depression and quality of life (QOL) among high school and university students. Literature search was performed in the Scopus, Embase, PubMed, Scielo, CINAHL and Web of Science databases, following the PRISMA methodology. The results were presented through descriptive approaches and meta-analysis. Thirty-six studies met the eligibility criteria, and twenty-six were included in the meta-analysis. The prevalence of depressive symptoms was 27% (95% CI 0.21-0.33) among students, being high school and university students was 25% (95% CI 0.14-0.37) and 27% (95% CI 0.20-0.34), respectively, and most studies have shown that depression was associated with low QOL. Among the limitations of the study is the difficulty of generalizing the results found, considering the large sample of health students. New studies should be conducted considering the severity, duration, and patterns of depressive symptoms in high school and university students, to better understand the relationship between depression and QOL.