Background: Whether there is an independent association between problem behaviours and substance use disorders (SUD) needs further investigation. This study examined prospective associations of adolescent psychopathology and problem behaviours with SUD in early adulthood, and whether these associations are confounded by other factors. Method: Data were from a prospective study of 2,429 young Australian adults from birth to the age of 21 when data on SUD were collected. Adolescent psychopathology and behaviour were assessed at 14 years via the Youth Self Report instrument on eight sub-scales of emotional and behavioural problems. Results: In multivariate analyses, attention problems, delinquency, and aggression were associated with both single and multiple SUD in early adulthood, with delinquent behaviour being the strongest predictor (OR = 2.0, 95% CI 1.4-2.9 for one SUD and OR = 3.6, 95% CI 2.4-5.0 for multiple SUDs). Conclusions: Problem behaviours, in particular delinquency and aggression in early adolescence predict long-term SUD. The results suggest that substance use prevention programs should target adolescents with early symptoms of psychopathology and problem behaviour.