The education sector offers compelling opportunities to address the shortcomings of traditional mental health delivery systems and to prevent and treat youth mental, emotional, and behavioral (MEB) problems. Recognizing that social and emotional wellness is intrinsically related to academic success, schools are moving to adopt multi-tier frameworks based on the public health model that provide a continuum of services to all children, including services to address both academic and MEB problems. In this article, we review the potential value of multi-tier frameworks in facilitating access to, and increasing the effectiveness of, mental health services in schools, and review the empirical support for school-based mental health interventions by tier. We go on to describe a community–academic partnership between the Seattle Public Schools and the University of Washington School Mental Health Assessment, Research, and Training (SMART) Center that exemplifies how multi-tier educational frameworks, research and evidence, and purposeful collaboration can combine to improve development and implementation of a range of school-based strategies focused on MEB needs of students. Finally, we present a set of 10 recommendations that may help guide other research and practice improvement efforts to address MEB problems in youth through effective school mental health programming.