Healthier school environments can benefit students, and school wellness policies may result in meaningful enhancements. Schools participating in federal child nutrition programs must implement wellness policies as mandated by law. The primary study objective is to assess effectiveness of implementing school-based nutrition and physical activity policies on student BMI trajectories. Cluster randomized trial using 2 × 2 factorial design. Twelve randomly selected schools in an urban district. Students were followed for 3 years through middle school, fifth to eighth grades (2011-2015, n=595 students, 92.3% participation, 85.2% retention). Specific to randomized condition, support was provided for implementation of nutrition policies (e.g., alternatives to food-based rewards/celebrations) and physical activity policies (e.g., opportunities for physical activity during/after school). Sex-/age-adjusted BMI percentile and BMI z-score; behavioral indicators. Data collected via standardized protocols. Analyses followed intention-to-treat principles, with planned secondary analyses (conducted 2016-2018). Students at schools randomized to receive support for nutrition policy implementation had healthier BMI trajectories over time (F=3.20, p=0.02), with a greater magnitude over time and cumulatively significant effects 3 years post-intervention (β=-2.40, p=0.04). Overall, students at schools randomized to receive the nutrition intervention had an increase in BMI percentile of <1%, compared with students in other conditions, whereas BMI percentile increased 3%-4%. There was no difference in student BMI between those in schools with and without physical activity policy implementation. Examining behavioral correlates in eighth grade, students at schools randomized to the nutrition condition consumed fewer unhealthy foods and sugar-sweetened beverages, and ate less frequently at fast-food restaurants (all p<0.03). This cluster randomized trial demonstrated effectiveness of providing support for implementation of school-based nutrition policies, but not physical activity policies, to limit BMI increases among middle school students. Results can guide future school interventions. This study is registered at www.clinicaltrials.gov NCT02043626.