On the eve of the 2020 Spring Festival, an epidemic of COVID-19 broke out in Wuhan and spread quickly across the country through population movements, posing a serious threat to Zhuhai and other large cities. In this paper, epidemiological survey data for 98 cases of COVID-19 published by the Zhuhai Municipal Health Bureau were used to analyze the spatio-temporal characteristics of 26 epidemic clusters, conduct case analyses of four types of typical transmission routes, and determine the spatio-temporal patterns and transmission routes of the virusin Zhuhai, with three main results. 1) The epidemic’s spread in Zhuhai was affected by timely population management and control in Wuhan, which restricted it to a limited range. 2) There were four different transmission paths: imported family cluster units, imported non-family cluster units, imported and local family cluster units, and imported and local non-family cluster units. The first unit was most important, though the path of non-family cluster transmission was especially complex; epidemiological investigations should be strengthened along with prevention and control measures. 3) For imported cases, given the lag time from importation to onset and the longest time interval between the onset of cluster units, a small number of cases or carriers can break the 14-day isolation limit currently in use, such that caution should be exercised regarding possible risks associated with this measure. Based on these, three recommendations can be made for the prevention and control of COVID-19. 1) It is necessary to fully estimate the risk of future epidemic spread that may be brought about by the movement of people returning to work following initial quarantine, while strengthening epidemiological studies, actively exploring the spatio-temporal law of population flow and epidemic spread, and using science-based methods to prevent and control further viral spread. 2) It is necessary to persist in the prevention and control of population movements from Hubei and other high-risk epidemic areas. The 14-days quarantine currently in place throughout the country is effective for the vast majority of cases or carriers of the virus, but the results show that a few can break this limit, suggesting that the isolation time should be prolonged by up to 24 days. 3) The combined use of epidemiological investigation and geographic information technology should be strengthened to improve the timely tracking of epidemic occurrence and spread, accurately identify the activities of high-risk groups, and conduct accurate and effective source tracing, prevention, and control. In short, for a major public health crisis like the COVID-19 outbreak, emergency management and control should involve many scientific fields (including medicine, geographic & information technology, computer science, psychology, and behavioral science) in order to achieve timely and effective prevention and control measures that rely on such multi-disciplinary joint action.