Black Americans have vastly increased odds and earlier onsets of stress- and age-related disease compared to White Americans. However, what contributes to these racial health disparities remains poorly understood. Using a sample of 1,577 older adults (32.7% Black; ages 55 to 65 at baseline), we examined whether stress, health behaviors, social isolation, and inflammation are associated with racial disparities in self-reported physical health. A latent cumulative stress factor and unique stress-domain specific factors were modeled by applying bifactor confirmatory analysis to assessments across the lifespan (i.e., childhood maltreatment, trauma exposure, discrimination, stressful life events, and indices of socioeconomic status). Physical health, health behavior and social isolation were assessed using self-report; interleukin-6 (IL-6) was assayed from morning fasting serum samples. A parallel serial mediational model tested whether Race (i.e., Black/White) is indirectly associated with health through the following 2 pathways: 1) cumulative stress. health behaviors, inflammation, and 2) cumulative stress, social isolation, and inflammation. There were significant indirect between race and self-reported physical health through cumulative stress, social isolation, and IL-6 (b = -.009, 95% CI: -.027, -.001) and cumulative stress, health behaviors, and IL-6 (b = -.018, 95% CI: -.044, -.005). Specifically, Black Americans were exposed to greater cumulative stress, which was associated with more social isolation as well as reduced preventive health behaviors; these in turn, were each independently associated with greater IL-6 and reduced physical health. Similar to the cumulative latent stress factor, a unique SES factor also indirectly linked race to physical health through these same two pathways (both bs < -.008, both 95% CI within: -.056, -.002). Cumulative stress exposure and socioeconomic status are indirectly associated with Black-White racial health disparities through behavioral (i.e., health behavior, social isolation) and biological (i.e., inflammation) factors. Currently, culturally responsive evidence-based interventions that enhance healthy stress coping and increased social connection are needed to directly confront health disparities. Ultimately, large scale anti-racist public policies (i.e., those which produce equitable outcomes) that reduce cumulative stress burden (e.g., a living wage, universal healthcare) may best attenuate racial health disparities.