Large-scale surveys have shown elevated risk for many indicators of substance abuse among Native American and Mixed-Race adolescents compared to other minority groups in the United States. This study examined underlying contextual factors associated with substance abuse among a nationally representative sample of White, Native American, and Mixed-Race adolescents 12-17 years of age, using combined datasets from the National Survey on Drug Use and Health (NSDUH, 2006-2009, N = 46,675, 48.77 % female). Native American adolescents displayed the highest rate of past-month binge drinking and past-year illicit drug use (14.06 % and 30.91%, respectively). Results of a logistic regression that included seven predictors of social bonding, individual views of substance use, and delinquent peer affiliations showed that friendships with delinquent peers and negative views of substance use were associated significantly with both substance abuse outcomes among White and Mixed-Race adolescents and, to a lesser extent, Native American adolescents. The association of parental disapproval with binge drinking was stronger for White than for Native American adolescents. Greater attention to specific measures reflecting racial groups’ contextual and historical differences may be needed to delineate mechanisms that discourage substance abuse among at-risk minority adolescent populations.