From December 31, 2019, a large-scale 2019 novel coronavirus disease (COVID-19) broke out in China. Tracking and analyzing the heterogeneity and effectiveness of cities’ prevention and control for COVID-19 epidemic is essential to design and adjust epidemic prevention and control. The number of newly infected cases in 25 China’s worst cities for COVID-19 epidemic from January 11 to February 10 was collected. The heterogeneity and effectiveness of these 25 cities’ prevention and control measures for COVID-19 were analyzed by using a estimate time-varying reproduction numbers method and a serial correlation method. The results shown that the effective reproduction number (R) in 25 cities showed a downward trend as a whole, but there was a significant difference in the R change trends among cities indicating that there was heterogeneity in the spread and control of COVID-19 in cities. Moreover, the COVID-19 control in 21 of 25 cities were effective and the risk of infection was decreasing due to their R had dropped below 1 on February 10, 2020 and the average decline of R in the past 5 days was greater than 0, while cities of Wuhan, Tianmen, Ezhou and Enshi were still difficult to effectively control the COVID-19 epidemic in a short period of time because their R was also greater than 1.