BACKGROUND: African American adolescents residing in the South are at increased risk for obesity and physical inactivity, yet our understanding of potential influences is limited. PURPOSE: Using an ecological framework, this study explored multilevel predictors (individual, family, home, and neighborhood environment) of moderate-to-vigorous physical activity (MVPA) among 116 African American adolescents (ages 12–16). METHODS: Adolescents and their parents completed self-report surveys for hypothesized predictors. Youth physical activity was measured using accelerometry. RESULTS: In multiple regression models, decreased daily MVPA was associated with female sex (β = −24.27, p < 0.0001). Family social support (β = 1.07, p = 0.004) and adolescent self efficacy for PA (β = 6.89, p = 0.054) were positively associated with daily MVPA. CONCLUSIONS: Adolescent demographics along with family social support and self-efficacy influence younger African American adolescent physical activity. Further exploration of the complex interaction of multiple levels of influence is needed to develop appropriate interventions for this vulnerable group.