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Background The coronavirus disease 2019 (COVID-19) has become a pandemic. Few studies have been conducted to investigate the spatio-temporal distribution of COVID-19 on nationwide city-level in China. Objective To analyze and visualize the spatiotemporal distribution characteristics and clustering pattern of COVID-19 cases from 362 cities of 31 provinces, municipalities and autonomous regions in mainland China. Methods A spatiotemporal statistical analysis of COVID-19 cases was carried out by collecting the confirmed COVID-19 cases in mainland China from January 10, 2020 to October 5, 2020. Methods including statistical charts, hotspot analysis, spatial autocorrelation, and Poisson space–time scan statistic were conducted. Results The high incidence stage of China’s COVID-19 epidemic was from January 17 to February 9, 2020 with daily increase rate greater than 7.5%. The hot spot analysis suggested that the cities including Wuhan, Huangshi, Ezhou, Xiaogan, Jingzhou, Huanggang, Xianning, and Xiantao, were the hot spots with statistical significance. Spatial autocorrelation analysis indicated a moderately correlated pattern of spatial clustering of COVID-19 cases across China in the early phase, with Moran’s I statistic reaching maximum value on January 31, at 0.235 (Z = 12.344, P = 0.001), but the spatial correlation gradually decreased later and showed a discrete trend to a random distribution. Considering both space and time, 19 statistically significant clusters were identified. 63.16% of the clusters occurred from January to February. Larger clusters were located in central and southern China. The most likely cluster (RR = 845.01, P Conclusions Spatio-temporal cluster detection plays a vital role in the exploration of epidemic evolution and early warning of disease outbreaks and recurrences. This study can provide scientific reference for the allocation of medical resources and monitoring potential rebound of the COVID-19 epidemic in China.