There is increasing research evidence that stressors in the social and physical environment (e.g., poverty, inadequate housing, air pollution, and racism) are associated with poor health outcomes. Given the complex set of determinants of health status, the disproportionate burden of disease experienced within marginalized communities, and the limited effectiveness of traditional prevention research, particularly within communities of color, there have been growing calls for more comprehensive and participatory approaches to public health research and practice. The purpose of this article is to describe and analyze the process of establishing, implementing, and evaluating the Detroit Community-Academic Urban Research Center (URC), a community-based participatory research (CBPR) partnership involving community-based organizations, a local health department, academia, and an integrated health care system. Lessons learned and recommendations for creating effective CBPR partnerships are presented.