This study examined whether the significant intervention effects of the Communities That Care (CTC) prevention system on youth problem behaviors observed in a panel of eighth-grade students (Hawkins et al. Archives of Pediatrics and Adolescent Medicine 163:789-798 2009) were mediated by community-level prevention system constructs posited in the CTC theory of change. Potential prevention system constructs included the community's degree of (a) adoption of a science-based approach to prevention, (b) collaboration on prevention activities, (c) support for prevention, and (d) norms against adolescent drug use as reported by key community leaders in 24 communities. Higher levels of community adoption of a science-based approach to prevention and support for prevention in 2004 predicted significantly lower levels of youth problem behaviors in 2007, and higher levels of community norms against adolescent drug use predicted lower levels of youth drug use in 2007. Effects of the CTC intervention on youth problem behaviors by the end of eighth grade were mediated fully by community adoption of a science-based approach to prevention. No other significant mediated effects were found. Results support CTC's theory of change that encourages communities to adopt a science-based approach to prevention as a primary mechanism for improving youth outcomes.