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American Indian (AI) communities have high levels of stress and trauma and are disproportionately affected by numerous preventable diseases. Here, we describe an academic–community partnership based on a collaboration between Blackfeet Community College students and faculty in Psychology and Immunology at Montana State University (MSU). The collaboration, which has spanned over 5 years, was sparked by community interest in the relationship between stress and disease on the Blackfeet reservation. Specifically, community members wanted to understand how the experience of psychological stress and trauma may affect disease risk in their community and identify factors that promote resilience. In doing so, they hoped to identify pathways through which health could be improved for individual community members. Here, we discuss all stages of the collaborative process, including development of measures and methods and themes of research projects, challenges for community members and non‐indigenous collaborators, future directions for research, and the lessons learned. Finally, we note the ways in which this partnership and experience has advanced the science of community engagement in tribal communities, with the hope that our experiences will positively affect future collaborations between indigenous community members and non‐indigenous scientists. Highlights: We describe the development of a biomedical program of research in a Tribal Community.We found that experiences varied across generations within the tribal community.Shifting the focus to resilience stimulated more community interest in the program of research. [ABSTRACT FROM AUTHOR]