Experiencing mental health stigma during adolescence can exacerbate mental health conditions, reduce quality of life and inhibit young people’s help-seeking for their mental health needs. For young people, education and contact have most often been viewed as suitable approaches for stigma reduction. However, evidence on the effectiveness of these anti-stigma interventions has not been consistent. This systematic review evaluated the effectiveness of interventions to reduce mental health stigma among youth aged 10–19 years. The review followed Cochrane and PRISMA guidelines. Eight databases were searched: PubMed, PsycINFO, MEDLINE, Web of Science, Scopus, EMBASE, British Education Index and CNKI. Hand searching from included studies was also conducted. Randomised controlled trials and experimental designs that included randomised allocation to interventions and control groups were included in the review. Narrative synthesis was employed to analyse the results. A meta-analysis was conducted to determine the effectiveness of included interventions. Twenty-two studies were included in the review. Eight studies reported positive effects, 11 studies found mixed effects and 3 studies reported no effect on indicators of mental health stigma among youth. Seven of the effective studies were education-based. Eleven studies were suitable for meta-analysis, and the multivariate meta-analytic model indicated a small, significant effect at post-intervention (d = .21, p < .001), but not at follow-up (d = .069, p = .347). Interventions to reduce stigma associated with mental health conditions showed small, short-term effects in young people. Education-based interventions showed relatively more significant effects than other types of interventions.