The authors tested hypothesized pathways from religiosity to adolescent substance use (tobacco, alcohol, and marijuana) with data from samples of middle school (n = 1,273) and high school students (n = 812). Confirmatory analysis of measures of religiosity supported a 2-factor solution with behavioral aspects (belonging, attendance) and personal aspects (importance, value, spirituality, forgiveness) as distinct factors. Structural modeling analyses indicated inverse indirect effects of personal religiosity on substance use, mediated through more good self-control and less tolerance for deviance. Religiosity was correlated with fewer deviant peer affiliations and nonendorsement of coping motives for substance use but did not have direct effects on these variables. Parental support and parent-child conflict also had significant effects (with opposite direction) on substance use, mediated through self-control and deviance-prone attitudes. Implications for prevention research are discussed.