<p>Substance use and delinquency are major public health concerns and are well-established, interrelated behaviours. However, in Latin America, and particularly in Argentina, research examining their relationship remains limited. This lack of evidence hinders the development of contextually relevant prevention and intervention strategies. This study analysed the associations between lifetime use of illicit substances and lifetime engagement in three types of offending among 2,370 high school students (50.5% male) who completed the International Self-Report Delinquency Study-4 (ISRD4) survey in Argentina. Substance use variables assessed lifetime cannabis use, other illicit drug use, and polysubstance use. Offending variables included property, violent, and versatile offending, with the latter defined as the engagement in three or more types of offences. Multivariate binomial logistic regressions were conducted by gender to examine the associations between substance use and each type of offending. Although substance use rates did not differ significantly by gender, males had higher odds of offending. Property and violent offending were significantly associated with cannabis use in both genders. Violent offending was also predicted by other illicit drug use among females and by polysubstance use among males. Versatile offending was associated with cannabis and polysubstance use among males and with other illicit drug use among females. These findings underscore a significant variability in the relationship between substance use and delinquency across genders, substance types, and offending behaviour, highlighting the importance of accounting for these variations when designing public policies to address these behaviours during adolescence.</p>