Regarding the damage evolution and reliability design of underwater connection structures, high-strength bolts were selected for tensile fatigue life testing. The crack propagation laws were analyzed using static stress intensity factor calculations and the Paris formula, and the simulation results were compared with the experimental results to verify the accuracy of the simulation model. For bolt-base connection structures, a reliability influence parameter analysis was conducted. The central composite design method was used to design the test points, and a response surface surrogate model was established to further optimize the design parameters. The optimized design results were verified using the Monte Carlo random sampling method, revealing that the optimized parameter combinations significantly reduced the maximum stress value of the structure and improved the reliability of the connection structure. The expected research results are expected to provide fundamental theoretical support for the safe and reliable operation of underwater vehicles.