Background The community-based participatory research (CBPR)-driven health needs assessment was a tool used to inform community-led, -implemented, and -sustained research and prevention strategies. Methods The Morehouse School of Medicine Prevention Research Center (MSM PRC) research and prevention initiatives are implemented in direct response to priorities identified through this process and tool. Led by a community-majority coalition board, the assessment coupled state and city secondary data with primary survey data collected by and from community residents. Results Hypertension, diabetes, obesity, and sexually transmitted infections were most frequently cited individual and community health priorities. Lack of social and family cohesion, limited or no opportunities to exercise, poor nutrition and lack of awareness and knowledge about diseases, and insufficient access to affordable health care were cited determinants of health priorities. Conclusions The CBPR-driven community health needs assessment (CHNA) informed and established a data-driven community engaged research agenda, policy, systems and environmental change approaches, community-led grants and job creation leveraging neighborhood contexts and strengths.