In this article we propose that nation-wide investment in mental and behavioral health (MBH) prevention efforts in public schools has the potential for powerful impact on developmental MBH in the United States (U.S.). We first provide an overview of the structure of public school systems in the U.S. Next, we apply the multi-tiered support system (MTSS) public health model to propose three key initiatives for optimal promotion of youth MBH through public schools in the U.S.: (a) universal access to high quality pre-kindergarten, (b) universal evidence-based social and emotional learning across all grades, and (c) universal MBH screening accompanied by tiered targeted and intensive support services. Within each proposed initiative, we summarize the evidence base and consider barriers and facilitators to implementation. We conclude that public schools in the U.S. represent an optimal place to promote children's and adolescents’ MBH in ways that prevent long-term mental and behavioral health problems. (author abstract)