To accurately assess the dynamic stability of the damaged ship, this paper performs an experimental campaign and presents a feasible numerical method to analyze the effects of microscopic air–fluid interactions on the motion responses of the damaged ship. The numerical approach can be applied to solve the coupled hydrodynamic behavior between the flooding process and the motion responses of the damaged ship. The volume of fluid (VOF) method was applied to capture the interface of the free surface, while the dynamic fluid–body Interaction (DFBI) morphing technique was applied to deal with mesh adaption. In particular, the UDF (user-defined field) function was activated to realize the initial distribution of the free surface. Firstly, by comparing the experimental and numerical results, the reliability of visualizing the flooding process and dealing with the motion responses of the damaged ship was efficiently verified. The numerical flooding process was able to reproduce the hydrodynamic phenomenon well, including the flooding jet, interaction, and flow between adjacent compartments. The numerical roll motion curve of the damaged ship was consistent with that predicted in the model test, with an error in roll amplitude of no more than 4%. Secondly, based on the verified numerical method, it was seen from the results with different ventilation positions that not only the air compressibility due to varying levels of ventilation cannot be neglected in damage assessment, but also the position of the ventilation hole was crucial. This was because different positions will create different paths for the compressed air to overflow and affect air–fluid interactions. Thus, the flooding force and air-impacting force acting on the internal hull will be different. In conclusion, this paper introduces a new consideration in the damage assessment of ships.