Despite the importance of pharmacies in ensuring medications and health care needs are met, there is limited up-to-date information regarding access to pharmacies or their services in the United States. To evaluate trends and disparities in access to pharmacies in 4 largest cities in the United States, New York City, Los Angeles, Houston, and Chicago, by neighborhood racial and ethnic composition from 2015 to 2020. Data from the National Council for Prescription Drug Programs (2015-2020) and the American Community Survey (2015-2019) were used. We examined neighborhoods (i.e., census tracts) and evaluated disparities in "pharmacy deserts" (low-income neighborhoods (1) whose average distance to the nearest pharmacy was at least 1 mile or (2) whose average distance to the nearest pharmacy was at least 0.5 mile and at least 100 households had no vehicle access). We also evaluated the differences in pharmacy closures and the availability of pharmacy services. From 2015 to 2020, the percent of neighborhoods with pharmacy deserts declined in New York City (from 1.6% to 0.9% of neighborhoods, P < 0.01), remained stable in Los Angeles (13.7% to 13.4%, P = 0.58) and Houston (27.0% to 28.5%, P = 0.18), and increased in Chicago (15.0% to 19.9%, P < 0.01). Pharmacy deserts were persistently more common in Black and Latino neighborhoods in all 4 cities. As of 2020, pharmacies in Black and Latino neighborhoods were also more likely to close and less likely to offer immunization, 24-hour, and drive-through services than pharmacies in other neighborhoods. To reduce disparities in access to medications and health care services, including those in response to the coronavirus disease 2019 pandemic (e.g., testing and vaccinations), policies that improve pharmacy access and expand the provision of pharmacy services in minority neighborhoods are critical.