Indigenous adolescents are overrepresented at multiple stages of the justice system, but we know very little about the role that mental health, particularly substance use disorder, plays in Indigenous pathways to arrest. This study examined the association between substance use disorder, its comorbidity with other disorders, and arrest using a longitudinal sample of Indigenous youth from the Northern Midwest and Canada. Of the 16% of youth who reported at least one arrest at Wave 5, half met criteria for substance abuse/dependence and slightly more for conduct disorder. Substance abuse/dependence and conduct disorder were each associated with an increased risk of arrest, although co-occurring disorders were not. The reciprocal effects of arrest and mental disorder are discussed.