This study examines the emotional and behavioural pathways to adolescent substance use and antisocial behaviour. Using a sample of 17,223 participants from the UK Millennium Cohort Study, we applied parallel-process growth mixture modelling on emotional and behavioural symptoms in those aged 3–14 and employed latent class analysis to identify patterns of substance use and antisocial behaviours at age 14. We then performed a multinomial regression analysis to explore the association between emotional and behavioural trajectories and patterns of adolescent substance use and antisocial behaviours, including sociodemographic, family, and maternal factors. We found five trajectories of emotional and behavioural symptoms and four classes of adolescence substance use and antisocial behaviour. Children and adolescents in the ‘high externalising and internalising’ and ‘moderate externalising’ trajectories were more likely to belong to any problematic behaviour class, especially the ‘poly-substance use and antisocial behaviours’ class. Inclusion in the ‘moderate externalising and internalising (childhood limited)’ class was associated with higher odds of belonging to the ‘alcohol and tobacco’ class. These associations remained significant after adjusting for important sociodemographic and contextual factors, such as maternal substance use, poverty, and parental status. Interventions on adolescent health promotion and risk behaviour prevention need to address the clustering of substance use and antisocial behaviour as well as the significant influence of early and chronic internalising and externalising symptoms on the aetiology of these behaviours.