This work evaluates the ability of cohesive zone modeling-based approaches to predict delamination in composite materials that develop large process zones under complex loading conditions. The R-curve effects subjected to static and fatigue loading under multiple loading modes, considering the loading history, are analyzed. To this end, the delamination predictions of a state-of-the-art CZM-based simulation strategy are evaluated by blind simulation of a validation benchmark test. The validation test promotes a non-self-similar delamination scenario, including a process zone that evolves under different loading mode conditions with a non-straight leading delamination front. Good delamination prediction accuracy is achieved. In addition, insights into the relationship between the features of the simulation strategy and the physics of the delamination process are discussed. With regard to the limitations of the simulation strategy, particular attention should be paid to modeling the contribution of an evolving process zone based on the loading mode history.