The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected Black and Latinx communities. Ecologic analyses have shown that counties with a higher percentage of Latinx and Black people have worse COVID-19 outcome rates. Few ecologic analyses have been published at the neighborhood (census tract) level. We sought to determine whether certain sociodemographic neighborhood ecologies were associated with COVID-19 case and death rates in metropolitan Atlanta, Georgia. We used census data and principal-component analysis to identify unique neighborhood ecologies. We then estimated correlation coefficients to determine whether the neighborhood profiles produced by a principal-component analysis were correlated with COVID-19 case and death rates. We conducted geographically weighted regression models to assess how correlation coefficients varied spatially for neighborhood ecologies and COVID-19 outcomes. We identified two unique neighborhood profiles: (1) high percentage of residents, Hispanic ethnicity, without a high school diploma, without health insurance, living in crowded households, and lower percentage older than 65 years; and (2) high percentage of residents, Black race, living in poverty, unemployed, and households receiving Supplemental Nutrition Assistance Program benefits. Profile 1 was associated with COVID-19 case rate (Pearson r = 0.462, P < 0.001) and profile 2 was associated with COVID-19 death rate (Spearman r = 0.279, P < 0.001). Correlations between neighborhood profiles and COVID-19 outcomes varied spatially. Neighborhoods were differentially at risk of COVID-19 cases or deaths depending on their sociodemographic ecology at the beginning of the COVID-19 pandemic. Prevention methods and interventions may need to consider different social determinants of health when addressing potential cases and deaths during future emergent epidemics.