African-American adolescents experience disproportionate rates of negative consequences of substance use despite using substances at average or below-average rates. Due to underrepresentation of African-American adolescents in etiological literature, risk and protective processes associated with their substance use require further study. This study examines the role of parental support in adolescents' conduct problems (CPs), depressive symptoms (DSs), and alcohol and marijuana use in a national sample and a high-risk sample of African-American adolescents. In both samples, parental support was inversely related to adolescent CPs, DSs, and alcohol and marijuana use. CPs, but not DSs, partially mediated the relation of parental support to substance use. Results were consistent across the national and high-risk samples, suggesting that the protective effect of parental support applies to African-American adolescents from a range of demographic backgrounds.