People with serious mental illnesses, particularly members of racial and ethnic minority groups, are rarely included in prioritizing research topics or developing the tools and measures important for improving their care. Community-based participatory research holds promise toward reducing mental health disparities. However, initiating research partnerships with community stakeholders is challenging and does not always lead to sustainable community health improvements. Using lessons learned from a project to improve understanding of patients' preferences and discrimination in depression and diabetes treatment, we describe barriers and facilitators to initiating a meaningful partnership with disenfranchised groups. Barriers fell within four domains: trepidation of community stakeholders, complex research methods, uncertainty among academic partners, and unclear partnership decision-making protocols. Primary facilitators included the meaningfulness of the research topic to the community, the presence of a well-established community-based organization, academic financial investment, co-learning activities, and flexibility. Successful initiation of these partnerships holds significant potential for addressing health care disparities.