Racial and ethnic-related health disparities in the United States have been intensified by the greater burden of Coronavirus Disease 2019 (COVID-19) in racial and ethnic minority populations. Compared to non-Hispanic White individuals, non-Hispanic Black and Hispanic/Latinx individuals infected by COVID-19 are at greater risk for hospitalization, intensive care unit admission, and death. There are several factors that may contribute to disparities in COVID-19-related severity and outcomes in these minority populations, including the greater burden of cardiovascular and metabolic diseases as discussed in our companion review article. Social determinants of health are a critical, yet often overlooked, contributor to racial and ethnic-related health disparities in non-Hispanic Black and Hispanic/Latinx individuals relative to non-Hispanic White individuals. Thus, the purpose of this review is to focus on the essential role of social factors in contributing to health disparities in chronic diseases and COVID-19 outcomes in minority populations. Herein, we begin by focusing on structural racism as a social determinant of health at the societal level that contributes to health disparities through downstream social level (e.g., occupation and residential conditions) and individual level health behaviors (e.g., nutrition, physical activity, and sleep). Lastly, we conclude with a discussion of practical applications and recommendations for future research and public health efforts that seek to reduce health disparities and overall disease burden.