AbstractRacial health disparities are a pervasive feature of modern experience and structural racism is increasingly recognized as a public health crisis. Yet evolutionary medicine has not adequately addressed the racialization of health and disease, particularly the systematic embedding of social biases in biological processes leading to disparate health outcomes delineated by socially defined race. In contrast to the sheer dominance of medical publications which still assume genetic ‘race’ and omit mention of its social construction, we present an alternative biological framework of racialized health. We explore the unifying evolutionary-ecological principle of niche construction as it offers critical insights on internal and external biological and behavioral feedback processes environments at every level of the organization. We Integrate insights of niche construction theory in the context of human evolutionary and social history and phenotype-genotype modification, exposing the extent to which racism is an evolutionary mismatch underlying inequitable disparities in disease. We then apply ecological models of niche exclusion and exploitation to institutional and interpersonal racial constructions of population and individual health and demonstrate how discriminatory processes of health and harm apply to evolutionarily relevant disease classes and life-history processes in which socially defined race is poorly understood and evaluated. Ultimately, we call for evolutionary and biomedical scholars to recognize the salience of racism as a pathogenic process biasing health outcomes studied across disciplines and to redress the neglect of focus on research and application related to this crucial issue.