African Americans are bearing a disproportionate burden of morbidity and mortality due to COVID-19 pandemic. To our knowledge, no previous study has delineated inequities potentially incentivized by systemic racism, and whether synergistic effects impose an abnormally high burden of social determinants of mental health on African American families in the era of COVID-19 pandemic. We applied the social ecological model (SEM) to portray inequities induced by systemic racism that impact the mental health of African American families. In our model, we identified systemic racism to be the primary operator of mental health disparity, which disproportionately affects African American families at all levels of the SEM. Programs tailored towards reducing the disproportionate detrimental effects of COVID-19 on the mental health of African Americans need to be culturally appropriate and consider the nuances of systemic racism, discrimination, and other institutionalized biases.