Abstract: To investigate the combined stress characteristics of a ship lock chamber-pile foundation system under asymmetric loading, this study takes a ship lock project on the main branch of the lower Ganjiang River as a case study. Using a three-dimensional finite element numerical simulation method, the deformation and stress responses of the lock chamber structure under completion, operation, maintenance, and check conditions were analyzed. The results show that under the completion condition (dominated by self-weight), the overall settlement of the lock chamber structure is significant, with the maximum settlement occurring at the middle of the lock chamber floor. This highlights the key role of load concentration and stiffness coordination in the central region. Under the operating condition, notable lateral displacement appears at the top of the gate wall, indicating that asymmetric loading significantly affects the lateral displacement of the water-retaining structure. Under the maintenance condition, compressive stress concentration is prominent in the junction area between the ship lock chamber and the pile foundation. The tensile stress at the corner of the lock wall under the check condition is more pronounced, suggesting that structural transition zones and geometric mutation areas are stress-sensitive parts. Additionally, the pile force is larger in areas with abrupt changes in load and stiffness. The research findings can provide a reference for the structural design and differential pile foundations treatment in similar ship lock engineering projects.