Bridges across waterways are susceptible to failure from ship collisions. Therefore, to provide a reference for bridge design and protection, reported here is a study of the response of a bridge pier during a collision with a barge. First, sphere–cylinder collision experiments were conducted in a water flume, and the fluid–structure interaction (FSI) method was implemented in the LS-DYNA software to simulate the collision process. The numerical and experimental values of the peak impact force agreed within 10%, thereby validating the FSI method for simulating the sphere–cylinder collision. Next, the FSI method was used to simulate the barge–pier collision process, in which the effects of barge mass, speed, collision angle, and location were considered. The simulated collision results of impact force, crush depth of barge bow, and displacement are summarized and discussed in detail. Unlike the constant added mass (CAM) method, the FSI method considers fluid–structure coupling and reproduces the collision phenomena whereby the barge stops upon collision and then goes into reverse. The water then propels the barge forward to collide with the pier repeatedly. Therefore, the FSI method is more effective for simulating barge–pier collisions.