Fully-coupled nonlinear dynamic analysis is increasingly used for assessing the seismic performance of pile-supported wharf structures subjected to liquefaction-induced lateral ground deformations. Several numerical challenges exist for analysis of this highly nonlinear soil-structure interaction, which require robust, yet practical, solutions that are validated with experimental data. This study presents a numerical model of a pile-supported wharf and evaluates the applicability of a soil constitutive model, and modeling assumptions and methods by using recorded data from a well-instrumented, large-scale centrifuge test. The objectives of this study include: (a) evaluating the performance of a recently developed pressure-dependent multi-yield surface constitutive soil model (PDMY03) to simulate the behavior of a liquefiable sand (b) assessing the effectiveness of a soil–pile interaction modeling approach in capturing the kinematic displacement demands on piles from a laterally spreading ground, and (c) evaluating the effectiveness and limitations of the 2D numerical model in approximating the 3D behavior of a wharf structure supported by multiple rows of piles, including the dynamic response of the centrifuge container. The implications of these assumptions and lessons learned from this study provide guidance for researcher modelers and practitioners for numerical modeling of similar soil–structure systems.