School connectedness is an important factor in the lives of youth and are a leverage point for optimizing youth's social, emotional, and physical health. This study presents a meta-analysis examining the relationship between school connectedness and four health domains that are prevalent in adolescence, have implications for adult health, and often co-occur: mental health, sexual health, violence, and high-risk substance use. Ninety articles published between 2009 and 2019 were included in the analysis. The study found that school connectedness had a protective average effect size across all health domains (Hedges' g = -0.345, p-value<0.001). When examined separately, school connectedness had a significant protective relationship with substance use (g = -0.379, p < 0.001), mental health (Hedges' g = -0.358, p < 0.001), violence (Hedges' g = -0.318, p < 0.001), sexual health (Hedges' g = -0.145, p < 0.001), and with co-occurring risks (Hedges' g = -0.331, p < 0.001). These results provide strong evidence that school connectedness has the potential to prevent and mitigate multiple health risks during adolescence.