Sexual activity and alcohol use continue to have negative effects on the well-being of today’s adolescents. This study used multiple regression analysis to examine relationships among personal factors, family factors, and adolescent sexual activity and alcohol use over three time points. Significant protective factors, which were inversely related to risky behavior, included general adolescent–mother communication, father and family connectedness, and disapproving parental attitudes towards sex. Permissive parenting was associated with self-efficacy for safe sex, early sexual initiation, and increased alcohol use. Health care providers should work to promote positive parent–child relationships and familial protective effects.