A systematic assessment of the effect of COVID-19 on the food retail environment—an important determinant of health—has not been conducted. Our objective was to assess the impact of COVID-19 on closures of restaurants, food retail stores, and fresh produce vendors in New York City (NYC). We conducted a cross-sectional study following the peak of COVID-19 in six neighborhoods in NYC. Two Chinese ethnic neighborhoods and four higher/lower resourced comparison neighborhoods were selected a priori based on 14 sociodemographic indicators. The primary outcome was indefinite/temporary closures or absence of food businesses. Of 2720 food businesses identified, produce vendors and restaurants were more likely to close than food retail stores. A higher proportion of food businesses closed in Chinese ethnic neighborhoods vs. comparison neighborhoods. COVID-19 impacted food businesses in six NYC neighborhoods examined in this period, with the greatest effect observed for Chinese ethnic neighborhoods.