Parental warmth and knowledge are protective factors against substance use, whereas parental psychological control is a risk factor. However, the interpretation of parenting and its effects on developmental outcomes may vary cross-culturally. This study examined direct and indirect effects of three parenting dimensions on substance use across Asian/Pacific Islander (API) and European Americans. A community sample of 97 API and 255 European Americans were followed from Grades 6 to 12. Participants reported on parenting in Grade 7, academic achievement and externalizing behaviors in Grades 7 and 8, and substance use behaviors in Grades 7, 9, and 12. Direct effects of parenting were not moderated by race. Overall, mother psychological control was a risk factor for substance use problems in Grade 9, whereas father knowledge was protective against alcohol use in Grade 9, substance use problems in Grades 9 and 12, and alcohol dependence in Grade 12. Moderated mediation analyses indicated significant mediational links among European Americans only: Mother knowledge predicted fewer externalizing problems in Grade 8, which in turn predicted fewer substance use problems in Grades 9 and 12. Father warmth predicted better academic achievement in Grade 8, which in turn predicted fewer substance use problems in Grades 9 and 12, as well as alcohol and marijuana dependence in Grade 12. Better academic achievement and fewer externalizing behaviors explain how positive parenting reduces substance use risk among European Americans. Promoting father knowledge of adolescents' whereabouts can reduce substance use risk among both European and API Americans.