Racial health inequities exemplified during the COVID-19 crisis have awakened a sense of urgency among public health and policy experts to examine contributing factors. One potential factor includes the socioeconomic disadvantage of racially segregated neighborhoods. This study quantified associations of neighborhood socioeconomic disadvantage in Chicago, Illinois, as measured by the Area Deprivation Index (ADI), with racial disparities in COVID-19 positivity. A retrospective cohort included 16,684 patients tested for COVID-19 at an academic medical center and five community-based testing sites during Chicago's "first wave" (March 12, 2020-June 25, 2020). Patients living in Black majority neighborhoods had two times higher odds of COVID-19 positivity relative to those in White majority neighborhoods. The ADI accounted for 20 percent of the racial disparity; however, COVID-19 positivity remained substantially higher at every decile of the ADI in Black relative to White neighborhoods. The remaining disparities (80 percent) suggest a large, cumulative effect of other structural disadvantages in urban communities of color.