Background: School-based health education can provide students with learning experiences that improve knowledge, attitudes, and perceptions (KAP) and behaviors regarding physical activity and nutrition. Methods: We conducted a 2-phase systematic review. Phase 1 was a review of reviews (ie, systematic reviews or meta-analyses) that were published 2010-2018. Phase 2 was a search for individual articles published 2010-2020 addressing topics relevant to our review; we searched for articles that had not been part of a sufficiently relevant or recent review or that had been part of a review that concluded that too few articles were available to assert sufficient evidence. Results: Forty-three studies were assessed: 20 randomized controlled trials and 23 quasi-experimental designs. Collectively, interventions had a favorable impact on students' PA and nutrition KAP, but behavioral and secondary outcome results (eg, body mass index) were mixed. Conclusions: Using the evidence-based health education strategies identified in this review can help contribute to improvements in students' KAP and behaviors.