Schools continue to be an important context for preventive interventions targeting a range of behavioral and mental health problems. Yet competing demands on teachers and shifting priorities in response to federal legislation have posed some unique challenges to prevention researchers working in school settings. This paper summarizes an approach to prevention partnerships developed over a decade and centered on the three-tiered Positive Behavioral Interventions and Supports (PBIS) model. A state-wide initiative was formed and led through a partnership between the Maryland State Department of Education, Sheppard Pratt Health System, and Johns Hopkins University, which focused on implementing evidence-based practices and conducting prevention research in Maryland public schools. Drawing on a community-based participatory research framework for developing research partnerships, we highlight the importance of forming and sustaining authentic relationships to support school-based prevention research and implementation of evidence-based programs. We also discuss how these relationships have been used to disseminate PBIS and rigorously test its effectiveness. We describe some lessons learned from the partnership and identify potential areas for future research on the prevention partnership model. We conclude with a discussion of the implications for both researchers and community partners engaged in translational research in school settings.