Over time, the uneven settlements of the structure and foundation are prominent in constructing ship lock heads on soft soil. These deformations endanger the safety of ship lock heads during construction. This research aimed to establish the ship lock head’s structural optimization procedure on soft soil, considering the time-varying effects of the structure and foundation. By comprehensively considering the linear viscoelastic creep of concrete and the elastoplastic consolidation characteristic of soft soil, a perfect time-dependent analysis method for the lock head on soft soil was proposed. Furthermore, a hybrid particle swarm optimization, enhanced whale optimization, and differential evolution (PSO-EWOA-DE) algorithm was proposed to optimize thirty-four design variables of a lock head. With the minimal volume of the lock head as the optimization objective, the finite element model was established. In the optimization process, three types of constraints were evaluated. The result showed that the optimized design could reduce 10.45% of structure volume. Through comparing and analysing the maximum principle stresses and vertical displacements of the lock head before and after optimization, some conclusions were drawn. The optimization procedure proposed in this paper provides a new perspective for the structural optimization of hydraulic structures on soft soil.