Evidence‐based research and interventions to address systemic institutional racism have never been more urgent. Yet, underrepresented minority (URM) professionals in research institutions who primarily produce that evidence have remained abysmally low for decades. This unique study of URM university professors assesses factors—vocational strain, role overload, discrimination, coping strategies—that contribute to health and well‐being, research productivity, and ultimately their retention in high impact research positions. We administered a web‐based survey assessing demographics, workplace stressors, perceived discrimination, life events, coping strategies, and physical and depressive symptoms. Study participants include 404 faculty of whom 254 are African Americans, 99 are Mexican Americans, and 51 are Puerto Ricans. Hierarchical regression analyses were employed to assess the associations between workplace stress, coping strategies, and symptoms. Results show that perceived discrimination, vocational strain, role overload, and life events directly affected physical symptoms, with self‐care (p < 0.001) moderating these effects. Vocational strain and life events had direct effects on depressive symptoms with self‐care (p < 0.05) and social support (p < 0.001) moderating these effects. Findings inform health care providers and university leaders about work stress and health conditions that may explain early morbidity and premature departures of URM faculty, and proffer institutional interventions to retain these faculty.