The objective was to analyze the longitudinal distribution, epidemiological characteristics, and local prevention and control measures of coronavirus disease 2019 (COVID-19) in six cities in Henan Province, China, from 21 January 2020 to 17 June 2020: Xinyang City (including Gushi County), Nanyang City (including Dengzhou City), Zhumadian City (including Xincai County), Zhengzhou City (including Gongyi City), Puyang City, and Anyang City (including Hua County). Data were collected and analyzed through the COVID-19 information published on the official websites of the health commissions in the six selected cities of Henan Province. As of 17 June 2020, the cumulative incidence rate of COVID-19 in Henan Province was 1.33/100,000, the cumulative cure rate was 98.27%, the cumulative mortality rate was 1.73%, the age range of diagnosed cases was 5 days to 85 years old, and the male-to-female ratio was 1.09:1. The confirmed cases of COVID-19 in Henan Province were mainly imported cases from Hubei, accounting for 87.74% of all cases, of which the highest proportion was 70.50% in Zhumadian. The contact cases and local cases increased in a fluctuating manner over time. In this paper, epidemiological characteristics of COVID-19 in Henan Province were analyzed from the onset of the outbreak to the effective control within 60 days, and effective and distinctive prevention and control measures in various cities were summarized to provide a favorable useful reference for the further formulation and implementation of epidemic prevention and control and a valuable theoretical basis for effectively avoiding a second outbreak.IMPORTANCE Epidemic prevention and control in China have entered a new stage of normalization. This article analyzes the epidemiological characteristics of COVID-19 in Henan Province and summarizes the effective disease prevention and control means and measures at the prefecture level; the normalized private data provide a theoretical reference for the formulation and conduct of future prevention and control work. At the same time, these epidemic prevention and control findings can also be used for reference in other countries and regions.