Considering the urgent need to increase vaccine uptake in Alabama, a rural state with the lowest rates of COVID-19 vaccination in the country, we conducted an exploratory study to elucidate sentiments toward vaccination among African American or black adolescents. We conducted in-depth interviews with 15–17 year olds in rural Alabama (N = 28). About 54% of our sample were female. Nearly a third lived with an older family member; 18% knew someone who contracted COVID-19. Using Rapid Qualitative Analysis, 3 COVID-19 vaccine-related themes emerged: influence of community leaders and older family members, fear of side effects and misinformation, and institutional distrust. To address COVID-19 vaccine hesitancy among rural African American or black adolescents, we suggest adopting a socioecological approach to public health messaging that addresses misinformation and government distrust and is delivered by local influencers with the social capital necessary to promote behavior change, namely older family members and Church officials.