There exists an urgent need to establish a system to simulate fatigue crack propagation in ship structures during their lifecycles. In the previous work, the authors have developed a simulation program, "CP-System", which can simulate fatigue crack propagation behavior by step-by-step finite element analyses. Although the developed program can reasonably predict fatigue crack lives and paths of a welded structure, it essentially supports only constant amplitude loading cases. In order to accurately evaluate the fatigue lives of ship structures, it is necessary to take into account wave-induced load histories, which are generally a kind of clustered loading with variable stress range. Under variable amplitude loading, the fatigue crack propagation behavior becomes apparently complex, which is significantly affected by load sequences. In the present paper, a new crack opening/closure simulation method is developed utilizing the crack tip stress field parameters evaluated by finite element analyses, and the effective stress intensity range, Delta K(RP), which precisely corresponds to the cyclic tensile plastic deformation ahead of the crack tip, is obtained by considering the plastic wake induced by fatigue crack propagation. In order to show an application of the developed program for marine structures, simulations of fatigue crack propagation in a ship structure subjected to water pressure are carried out assuming random sequence of six clustered loading patterns. From the results of the simulations, it is shown that the fatigue crack lives of ship structures may be significantly retarded by load interaction effects, so that the conventional method for fatigue life assessment may cause a rather conservative fatigue life estimation of a ship structure.