Despite evidence that American Indian (AI) adolescents are disproportionately involved in crime and delinquent behavior, there exists scant research exploring the correlates of crime among this group. We posit that Agnew’s General Strain Theory (GST) is well suited to explain AI delinquent activity. Using the National Longitudinal Study of Adolescent Health, we examined a subsample of AI students—a study that represents, to the best of our knowledge, the initial published test of GST principles used to explain AI delinquent behavior. Overall, we find mixed support for the core principles of GST applying to AI delinquent behavior. We also found evidence that some of the personal and social resources identified by Agnew condition the strain–delinquent behavior relationship, albeit, sometimes in ways that are not entirely consistent with GST.