Health care in the United States has seen many great innovations and successes in the past decades. However, to this day, the color of a person’s skin determines—to a considerable degree—his/her prospects of wellness; risk of disease, and death; and the quality of care received. Disparities in cardiovascular disease (CVD)—the leading cause of morbidity and mortality globally—are one of the starkest reminders of social injustices, and racial inequities, which continue to plague our society. People of color—including Black, Hispanic, American Indian, Asian, and others—experience varying degrees of social disadvantage that puts these groups at increased risk of CVD and poor disease outcomes, including mortality. Racial/ethnic disparities in CVD, while documented extensively, have not been examined from a broad, upstream, social determinants of health lens. In this review, we apply a comprehensive social determinants of health framework to better understand how structural racism increases individual and cumulative social determinants of health burden for historically underserved racial and ethnic groups, and increases their risk of CVD. We analyze the link between race, racism, and CVD, including major pathways and structural barriers to cardiovascular health, using 5 distinct social determinants of health domains: economic stability ; neighborhood and physical environment ; education ; community and social context ; and healthcare system . We conclude with a set of research and policy recommendations to inform future work in the field, and move a step closer to health equity.