<p>Adolescent substance use remains a significant public health concern and is associated with future negative outcomes. Risk factors for the development of adolescent substance use behaviours include the presence of externalizing and/or internalizing problems; however, previous studies have not always considered their co-occurring influences. This study aims to better understand the role of externalizing and internalizing problems in the development of adolescent substance use using a person-centred approach. Participants were drawn from an ongoing longitudinal study of children with and without early conduct problems (<i>N</i> = 744). Externalizing and internalizing problems were measured annually using teacher and parent reports from study inception to 7&#xa0;years later. Substance use outcomes were measured using self-report when participants were approximately 17&#xa0;years old. Latent class growth analyses identified four trajectory classes: (i) a decreasing externalizing co-occurring trajectory characterised by clinical and at-risk levels of both externalizing and internalizing problems, (ii) a high stable co-occurring trajectory characterised by clinical levels of externalizing problems and at-risk/clinical levels of internalizing problems, (iii) an at-risk externalizing trajectory characterised by at-risk levels of externalizing problems and non-clinical levels of internalizing problems, and (iv) a non-clinical trajectory. Youth in the high stable externalizing co-occurring trajectory were significantly more likely to report substance use behaviours and consequences when compared to other developmental trajectories, including the decreasing externalizing co-occurring trajectory. Our results suggest that the highest risk for substance use remains with those who follow a trajectory with high and stable externalizing problems. Early prevention and intervention efforts targeting externalizing problems could help decrease one’s future risk of engaging in substance use.</p>