Racial disparities in health are a major public health problem in the United States, especially when comparing chronic disease morbidity and mortality for Black versus White Americans. These health disparities are primarily due to insidious anti-Black racism that permeates American history, current culture and institutions, and interpersonal interactions. But how does racism get under the skull and the skin to influence brain and bodily processes that impact the health of Black Americans? In the present article, we present a model describing the possible neural and inflammatory mechanisms linking racism and health. We hypothesize that racism influences neural activity and connectivity in the salience and default mode networks of the brain and disrupts interactions between these networks and the executive control network. This pattern of neural functioning in turn leads to greater sympathetic nervous system signaling, hypothalamic-pituitary-adrenal axis activation, and increased expression of genes involved in inflammation, ultimately leading to higher levels of proinflammatory cytokines in the body and brain. Over time, these neural and physiological responses can lead to chronic physical and mental health conditions, disrupt well-being, and cause premature mortality. Given that research in this area is underdeveloped to date, we emphasize opportunities for future research that are needed to build a comprehensive mechanistic understanding of the brain-body pathways linking anti-Black racism and health. (PsycInfo Database Record (c) 2023 APA, all rights reserved).