This thesis synthesizes a body of published research spanning fifteen years. It investigates the challenges and necessary supports for moving the ever-evolving body of prevention science to application in policy and practice, in order to prevent delinquency and youth risk-taking behavior. Through the publications and the summary chapter and overview, the thesis offers a coherent narrative of the development of this body of research: from the identification of preventive interventions with demonstrated evidence of effectiveness; to enumerating the barriers to taking evidence-based prevention programs (EBPs) to scale; to understanding the challenges of implementation fidelity, quality, and adaptation as major barriers to practice at scale; to identifying the predictors of sustainment and translating this knowledge into practice; to the development of system capacity and a state- level infrastructure (the EPISCenter) to address these challenges and to sustain EBPs effectively at a whole-of-population level.