Parental social support and monitoring are associated with children’s externalizing behavior but clarity is needed on how these mechanisms interact to influence youth. This study examined if parental social support magnifies the protective effects of sources of parental knowledge (Parental Control, Parental Solicitation, Child Disclosure) on the development of substance initiation and delinquency across adolescence. Participants were 6–8th graders (N = 1023; 52% female; 83% White; 87.8% non-Hispanic) from six (one urban, two rural, three suburban) Rhode Island schools assessed annually for four years. Parental control protected against substance initiation, but only in supportive relationships. All sources of parental knowledge were associated with less delinquency, but only in supportive relationships. Interventions focused on increasing children’s perceptions of parental social support may enhance the effectiveness of sources of parental knowledge in buffering against children’s externalizing behavior.