Strengthening the infectious disease prevention and control system at the frontier ports of China is the top priority of biosecurity considering the frequent outbreak of infectious diseases worldwide. This study analyzed the current status of biosecurity defense capabilities and systems at frontier ports of China from the aspects of biosafety status, sanitary and quarantine lines, and organizational structure for infectious disease prevention and control at ports. It also explored the weaknesses regarding the prevention and control of infectious disease at frontier ports through the comparison with European countries and the United States. Specifically, problems exist, including multi-sector and piecemeal management, decentralized formulation of the infectious disease surveillance and early warning network, deficiency in biosecurity situation perception, and uneven level of port health and quarantine capacities. Furthermore, several suggestions were proposed. First, an inter-departmental mutual-recognition mechanism needs to be established and the normalization of an infectious disease joint prevention and control mechanism should be promoted, thus to enhance information sharing among departments. Second, it is necessary to build infectious disease monitoring sites overseas, establish a mechanism of health and quarantine officers, improve outbound biosecurity risk monitoring by establishing a multipoint-trigger early-warning mechanism, and actively participate in the international public-health cooperation network. Third, we should strengthen the capacities of port laboratories to detect and identify pathogens, promote the development of testing equipment suitable for frontier port application scenarios, and accelerate the construction of a frontier port biosecurity resource bank.