The global spread of COVID-19 has led to profound reflection on building a global public health security system. This paper uses the urban data collected during the COVID-19 epidemic in China in 2020 to evaluate the effect of the National Sanitary City (NSC) policy on the prevention and control of that epidemic at different stages. We found that the NSC policy was able to curb the occurrence and transmission of the epidemic the epidemic effectively after controlling a series of factors such as urban characteristics, population mobility and pathogen transmission. Compared with non-NSCs, the NSCs were better able to control the number of infected people and the infection rate and transmission rate, and this performance was even more impressive when the epidemic gradually entered the sporadic distribution stage. The heterogeneity analysis shows that the impact of the NSC policy on the prevention and control of COVID-19 differs according to the economic development level and population size. To a certain extent, the NSC policy has blocked the spread of viruses by continuously improving the urban medical and health system and strengthening the publicity concerning infectious disease prevention and control knowledge.