Population mobility affects the spread of the new coronavirus and of risk. Based on Baidu migration big data and provinces and municipalities’ health committee data, combined with geographic information technology, this paper studies the spatial relationship between the spread of Corona Virus Disease 2019(COVID-19) in 136 cities from January 1st to March 5th, 2020, and the outflow of population in Wuhan, which impacted urban public health management in China. The following results were obtained. The spread of COVID-19 in China has the following stages and characteristics: occurrence and recessive spread, rapid spread and outbreak, diffusion containment, and diffusion attenuation. From January 1st to March 5th, 2020, it was observed that the population flow of Wuhan City mainly extends to the Hubei Province and its surrounding provinces and cities, as well as Beijing, Shanghai, Guangzhou, Shenzhen and other first-tier cities, with geographical proximity and characteristics similar to regional central city population inflow. Influenced by geographical distance, time cost, social and economic connection, overseas input, and so on, the spatial distribution of COVID-19 is evidently unbalanced. The urban agglomeration in the middle reaches of the Yangtze River, the Beijing-Tianjin-Hebei urban agglomeration, the Yangtze River Delta urban agglomeration, Guangdong-Hong Kong-Macau Greater Bay Area, and the Chengdu-Chongqing urban agglomeration have become key areas for the concentrated distribution of COVID-19. Additionally, some key entry and exit port cities present a higher risk of spreading. A strong positive grade correlation between epidemic spread and population outflow is observed with COVID-19. The spatial relationship between the two can be divided into eight regulation types. Nearly 90% of cities have the characteristics of large population inflow, high numbers of confirmed cases or small population inflow, and low numbers of confirmed cases. Among these, cities with large population inflow and high numbers of confirmed cases are mainly concentrated in the Hubei Province and central cities of key urban agglomerations in China. The pressure of prevention and control stems from the risk of epidemic spread, caused by a large population inflow and high number of confirmed cases. The urban distribution, with a small population inflow and low number of confirmed cases, is scattered, and the difficulty involved in prevention and control is the improvement of the precision of such countermeasures. Although China’s strategies for epidemic prevention and control have achieved remarkable results, considering the evolution of the global epidemic situation, rebound uncertainty still exists, and external defense input as well as internal defense rebound pressure are still very heavy. Currently, and in the future, the prevention and control of the epidemic situation will become the “new normal” with the economic and social development of our country. Improving the capacity for urban public health management is necessary for the prevention and control of the epidemic situation in China, especially in the future. Chinese epidemic prevention and control should still consider local conditions and formulate targeted prevention and control strategies. In particular, it is necessary to consider the relationship between the spread of COVID-19 and population flow, economic ties, transportation costs, international exchanges and other factors, and set specific classifications and control plans. To facilitate the joint prevention and control strategy to formulate full coverage, and “Not One Less,” we should not only approach the current epidemic prevention and control it from a dynamic perspective, but also consider epidemic prevention and control work in specific types of cities. Urban agglomeration areas and port cities often have a large population inflow, frequent economic ties, high economic development pressure, and high-risk epidemic prevention and control. They bear the dual responsibility of economic and social development, stability, epidemic prevention, and control and management. In the context of resuming production, work, and economic and social recovery, special attention should be paid to the regular prevention and control of the epidemic situation as well as the improvement of urban public health management capacities.