A relatively new area of research suggests that naturally occurring mentoring relationships may influence the development of adolescents by protecting against risk behaviors. Few studies have explored how these relationships function to reduce risk behavior among youth, especially in the school context. Based on previous research and theory, we proposed and tested a mediation model, which hypothesized that school attachment mediated the longitudinal association between school-based natural mentoring relationships and risk behaviors, including eight indicators of substance use and violence. Students (N = 3320) from 65 high schools across eight states completed a self-report questionnaire at baseline and 1-year follow-up. The sample was comprised of youth with an average age of 14.8 years and an almost equal percentage of females (53%) and males from various ethnic backgrounds. Tests for mediation were conducted in Mplus using path analysis with full information maximum likelihood procedures and models adjusted for demographic covariates and baseline level of the dependent variable. Results suggested that natural mentoring relationships had a protective indirect influence on all eight risk behaviors through its positive association on the school attachment mediator. Implications are discussed for strengthening the association between school-based natural mentoring and school attachment to prevent risk behaviors among youth.