Seaports function as lifeline systems in maritime transportation, facilitating critical processes like shipping, distribution, and allied cargo handling. These diverse subsystems constitute the Port Infrastructure System (PIS) and have intricate functional interdependencies. The PIS is vulnerable to several external disruptions, and the impact of COVID-19 is severe and unprecedented in this domain. Therefore, this study proposes a novel general port safety framework to cope with recurring hazards and crisis events like COVID-19 and to augment PIS safety through a multi-state failure system. The PIS is divided into three critical subsystems: shipping, terminal, and distribution infrastructure, thereby capturing its functional interdependency and intricacy. A dynamic input–output model is employed, incorporating the spatial variability and average delay of the disruption, to determine the PIS resilience capacity under the stated disruptions. This study simulates three disruption scenarios and determines the functional failure capacity of the system by generating a functional change curve in Simulink. This study offers viable solutions to port managers, terminal operators, and concerned authorities in the efficient running of intricate interdependent processes and in devising efficient risk control measures to enhance overall PIS resilience and reliability. As part of future studies, given the difficulty in obtaining relevant data and the relatively limited validation of the current model, we aim to improve the accuracy and reliability of our model and enhance its practical applicability to real-world situations with data collected from a real-world case study of a PIS system.