The motion stability of the Unmanned Surface Vessel (USV) is threatened by the action of waves under a rough sea state. In the present paper, the motion of a large-scale USV is numerically simulated under high sea state of level 5 and 7. The overset grid method and Reynolds Averaged Navier–Stokes (RANS) approach are employed to solve Navier–Stokes (N-S) equations. For the case of wave incident angle 0° and 30°, the heave, pitch and roll motion response of a large scale USV are investigated by using the six Degrees of Freedom (6-DOF) numerical model. The effects of different sea states, as well as different wave directions, on the motion of USV are compared. The comparative results indicate that the response of this USV in waves is the periodic free-motion according to the corresponding amplitude, which does not exceed the stable range, and there are no overturning and other situations that may affect the safety, in the case of level 5 and 7 sea states. The corresponding pressure at the bottom of this USV meets the range of material strength, and no structural damage or injury to the hull occurs, although the pressure varies at different wave periods. For the case of different wave directions, the analysis of the boundary layer thickness shows that the wave direction is of great importance to the boundary layer thickness distribution, both in the level 5 and level 7 sea states.