Multi-body separation involving collisions is common in aerospace engineering. The ability to analyze the dynamics of multi-body collisions is rarely possessed by traditional Multi-Body Separation Simulation (MBSS) methods. To methodically address this challenging issue, a research study is conducted herein based on the MBSS in conjunction with an efficient and high-accuracy collision model. First, an MBSS based on the dynamic unstructured overset grid method is performed by solving the unsteady compressible Reynolds-averaged Navier-Stokes equations with the six-degree-of-freedom rigid-body motion. Second, to detect object collisions and calculate collision factors with high accuracy and efficiency, a collision detection approach and a nearest distance calculation based methodology on the basis of computational fluid dynamics data structures and bounding volume hierarchies are originally proposed. Third, a transient multiple collision model is established to simulate an unlimited number of object collisions within a single time step. Finally, collision simulation experiments with balls and those of the space shuttle’s collision with foreign objects are conducted to verify the accuracy, efficiency, and robustness of the newly developed approach.