The practical engineering structures are not always perpendicular to the wind but often in skew positions. This yawed configuration may lead to more complex three-dimensional flow characteristics and different vortex-induced vibration (VIV) responses. However, the related study is very inadequate. Therefore, comprehensive numerical investigations of the VIV characteristics of a 4:1 rectangular cylinder have been conducted using the three-dimensional (3D) Large-Eddy Simulation (LES) at five different yaw angles (β = 0°, 5°, 10°, 20°, 30°). An innovative method for creating 3D meshes was introduced, demonstrating a good agreement with the experimental results while significantly reducing the mesh number, and consequently the computation time. The VIV response, pressure distribution, aerodynamic force, flow field, and energy input/output were analyzed for various yaw angles. The results demonstrate that the periodic boundary conditions on the spanwise domain side is more reliable than those of the wall boundary conditions. The velocity component parallel to the cylinder axis can be ignored in the analysis of elastically-mounted rectangular rigid cylinders for β up to 30°. If only considering the perpendicular axis velocity component, the amplitudes and lock-in regions for β = 5°, 10°, 20°, and 30° are highly consistent with those of β = 0°, which have effectively validated the accuracy of Independence Principle in evaluating the VIV of a 4:1 rectangular cylinder.