Introduction Applying an intersectional framework, we examined sex and racial inequality in COVID-19–related employment loss (ie, job furlough, layoff, and reduced pay) and food insecurity (ie, quality and quantity of food eaten, food worry, and receipt of free meals or groceries) among residents in Saint Louis County, Missouri. Methods We used cross-sectional data from adults aged 18 or older (N = 2,146), surveyed by using landlines or cellular phones between August 12, 2020, and October 27, 2020. We calculated surveyweighted prevalence of employment loss and food insecurity for each group (Black female, Black male, White female, White male). Odds ratios for each group were estimated by using surveyweighted binary and multinomial logistic regression models. Results Black female residents had higher odds of being laid off, as compared with White male residents (OR = 2.61, 95% CI, 1.24–5.46). Both Black female residents (OR = 4.13, 95% CI, 2.29–7.45) and Black male residents (OR = 2.41, 95% CI, 1.15–5.07) were more likely to receive free groceries, compared with White male residents. Black female (OR = 4.25, 95% CI, 2.28–7.94) and White female residents (OR = 1.93, 95% CI, 1.04–3.60) had higher odds of sometimes worrying about food compared with White male residents. Black women also had higher odds of always or nearly always worrying about food, compared with White men (OR = 2.99, 95% CI, 1.52–5.87). Conclusion Black women faced the highest odds of employment loss and food insecurity, highlighting the disproportionate impact of COVID-19 among people with intersectional disadvantages of being both Black and female. Interventions to reduce employment loss and food insecurity can help reduce the disproportionately negative social effects among Black women.