Aim: This study aimed at determining the association of father's and mother's (parental) substance use disorder (SUD) and discipline styles and son's neurobehavior disinhibition (ND) with son's SUD from childhood (age 10–12) to young adulthood (age 19). It was hypothesized that (1) parental discipline styles and son's ND mediate the association between parental SUD and son's SUD, (2) son's ND mediates the association between parental discipline styles and son's SUD, and (3) parental discipline styles mediate the association between ND and SUD in the son. Methods: Two-hundred-sixty-three families including a 10–12 year-old son and both parents participated in the study. Results: (1) mother's discipline styles predicted father's discipline styles, (2) son's ND predicted mother's instilling guilt positively and father's punishment negatively, (3) son's ND mediated the association between father's SUD and punishment and son's SUD, and (4) mother's SUD predicted son's ND and SUD. Conclusions: The reciprocal prediction between son's ND and father's punishment and prediction of father's punishment by mother's punishment point to the need for family-based interventions that take into account the quality of specific dyadic interactions pertaining to discipline behaviors that amplify the risk for SUD in male children.