Unsteady cavitating flows around propellers become increasingly prominent on large-scale and high-speed ships, but large eddy simulations (LES) are limited in the literature. In this study, numerical simulation of an unsteady cavitating flow around a highly skewed propeller in a nonuniform wake is performed based on an explicit LES approach with subgrid model. Kunz cavitation model, volume of fluid (VOF) method, and a moving mesh scheme are adopted. The predicted evolution of the unsteady cavitating flow around a highly skewed propeller in a nonuniform ship wake is in good agreement with experimental results. An analysis of the factors affecting the cavitation on the propeller is conducted based on numerical simulation. Furthermore, the influences between cavitation structures and vortex structures are also briefly analyzed.