OBJECTIVES: Whole-school interventions that promote student commitment to school are a promising modality to reduce health inequalities through school-level change; however, evidence for the effectiveness of these interventions in improving policy-relevant health outcomes, such as substance use and violence, has not been comprehensively synthesised. STUDY DESIGN: This was a systematic review and meta-analysis. METHODS: We searched 20 databases and a range of other sources to identify randomised trials meeting our intervention definition and reporting substance use and violence outcomes. Extracted effect estimates were meta-analysed using robust variance estimation with random effects, separating effects <1 year from baseline and effects at or more than 1 year from baseline. RESULTS: We included 18 evaluations with varying risk of bias. Pooled effects suggested significant impacts on short-term (odds ratio [OR] = 0.85, 95% confidence interval [CI] 0.76, 0.96) and long-term (OR = 0.79, 95% CI 0.65, 0.98) violence perpetration, short-term (OR = 0.84, 95% CI 0.72, 0.98) and long-term (OR = 0.85, 95% CI 0.73, 0.99) violence victimisation, and short-term (OR = 0.83, 95% CI 0.70, 0.97) and long-term (OR = 0.79, 95% CI 0.62, 0.998) substance use outcomes, with effects relatively stable between short-term and long-term analyses. Stratifying substance use meta-analyses by type (e.g. smoking, alcohol) did not impact results. All meta-analyses had substantial heterogeneity. CONCLUSION: Although diverse in content, interventions appear effective with respect to the review outcomes and as a form of universal prevention. Future research should consider contextual contingencies in intervention effectiveness, given considerable policy and practice interest in these interventions and the need to support schools in effective decision-making as to intervention choice.