What is already known on this topic? African Americans are more likely to contract coronavirus disease 2019 (COVID-19), be hospitalized for it, and die of the disease when compared with other racial/ethnic groups. Psychosocial, sociocultural, and environmental vulnerabilities, compounded by preexisting health conditions, exacerbate this health disparity. What is added by this report? This report adds to an understanding of the interconnected historical, policy, clinical, and community factors associated with pandemic risk, which underpin community-based participatory research approaches to advance the art and science of community engagement among African Americans in the COVID-19 era. What are the implications for public health practice? When considered together, the factors detailed in this commentary create opportunities for new approaches to intentionally engage socially vulnerable African Americans. The proposed response strategies will proactively prepare public health leaders for the next pandemic and advance community leadership toward health equity.