Coronavirus disease 2019 (COVID-19) is a novel infectious disease that has spread worldwide. In the United States, COVID-19 disproportionately affects racial and ethnic minorities, particularly African Americans, with an observed 2-fold higher rate for hospitalization and greater than 2-fold higher rate for death as compared with White Americans. The disparity seen with COVID-19 is consistent with patterns of disparities observed for cancer; it is well documented that 5-year survival rates for multiple cancers are lower in African Americans compared with White Americans. Root cause contributions for the disparity overlap between COVID-19 and cancer. While cancer is a genetic disease that is influenced by tissue microenvironment, COVID-19 is an infectious disease that is enabled by cellular expression of angiotensin-converting enzyme 2 receptors. However, socioeconomic disadvantages, level of education, lifestyle factors, health comorbidities, and limited access to medical care appear to fuel underlying risk for both cancer and COVID-19 disparities. In addition to African Americans demonstrating higher risk of acquiring and dying from either disease, they are underrepresented in clinical trials involving cancer or COVID-19. Long-term disparities are present with survivorship from cancer and may be likely with survivorship from COVID-19; both have revealed untoward effects on postdiagnosis economic viability for African Americans. Collaborative strategies that include community engagement, diverse participation in cancer and COVID-19 clinical trials, providing insurance for affected persons who lost employment due to either disease, and supporting safety-net and public hospitals for health care access will be critical to stem these disparities.