The present study examined i) the direct association between traumatic brain injury (TBI) in childhood and conduct disorder symptoms in adolescence, ii) whether this effect is mediated by impulsivity and/or callous unemotional traits (CU traits), and iii) whether these indirect effects are moderated by childhood family adversity and adolescent substance use. Utilising data from the Avon Longitudinal Study of Parents and Children (ALSPAC), participants with head injury information up to 12 years (4.5 years, 5.4 years, 6.5 years, 8.6 years, 11.7 years) were identified and categorised into a TBI (n = 409), orthopaedic injury (n = 1469) or non-injury group (n = 5685). Psychosocial factors such as impulsivity at 13 years, CU traits at 13 years, childhood family adversity (between birth to 4 years) and substance use at 14 years were collated for moderated mediation analyses. Conduct disorder symptoms were assessed at 16 years of age. TBI and conduct disorder symptoms were positively associated, and this association was mediated by impulsivity but not CU traits. The indirect effects were higher in magnitude for individuals with higher levels of childhood family adversity. Adolescent substance use was not found to moderate the indirect effects between TBI and conduct disorder symptoms. These results were specific to TBI individuals, and not in participants with orthopaedic injury and no reported injuries. Targeting impulsivity and early family adversity may alleviate the risk of conduct disorder symptoms following TBI in childhood. These findings have important implications for informing neuro-rehabilitative and preventative measures in clinical and community settings.