Background: Adolescent juvenile offenders are at high risk for problems associated with drug use, including polysubstance use (i.e., use of a variety of drugs). The combination of juvenile offending and polysubstance use presents a significant public and child health concern. Objective: This study explored polysubstance use among a sample of youth incarcerated for serious offenses. We examined several risk factors for substance use and delinquency (i.e., early and frequent substance use, prior history of arrests, school expulsion, Black ethnicity), as well as the association between aggression and polysubstance use. Methods: Data were collected via questionnaires from 373 serious male juvenile offenders upon intake into a secure locked facility. Youth were on average 16 years old, and minority youth were overrepresented (28.1% Black, 53.1% Latino). Poisson regressions were used to assess the associations between the risk factors, aggression, and polysubstance use. Results: Consistent with the literature, Black youth reported less polysubstance use and later age of drug use onset than White and Latino youth. Findings suggest that Latino juvenile offenders and those with an early and problematic pattern of substance use are at heightened risk for polysubstance use. Aggression was not significantly related to polysubstance use, over and above the risk factors. Conclusions: Given that Latino youth experience low rates of treatment for substance use, the development of culturally-sensitive interventions for these youth is needed. Interventions should also be multifaceted to address the multitude of risk factors associated with polysubstance use among juvenile offenders.