Background: HealthCorps provides school wellness programming using curricula to promote changes in nutrition, mental health, and physical activity behaviors. The research objective was to evaluate effects of implementing its curricula on nutrition, mental health, and physical activity knowledge and behavior. Methods: Pre- and postsurvey data were collected (N = 2255) during the 2012-2013 academic year from 14 New York City public high schools. An 18-item knowledge questionnaire addressed 3 domains; 26 behavioral items were analyzed by factor analysis to identify 6 behavior domains, breakfast being a seventh 1-item domain. We examined the effects stratified by sex, applying mixed-effects models to take into account clustering effects of schools and participants adjusted for age. Results: The HealthCorps program significantly increased all 3 knowledge domains (p < 0.05), and significantly changed several key behavioral domains. Boys significantly increased fruits/vegetables intake (p = 0.03). Girls increased acceptance of new fruits/vegetables (p = 0.03) and breakfast consumption (p = 0.04), and decreased sugar-sweetened beverages and energy dense food intake (p = 0.03). The associations between knowledge and behavior were stronger in boys than girls. Conclusion: The HealthCorps program significantly increased participants' knowledge on nutrition, mental health, and physical activity. It also improved several key behavioral domains, which are targets of the 2010 Dietary Guidelines to address obesity in youth.