Thick airfoils are conventionally adopted in the blade root region of a wind turbine to ensure structural safety under extreme conditions, despite the resulting power loss. To prevent this loss, a passive flow control device known as a vortex generator (VG) is installed at the starting point of the stall to control the flow field near the wall of the suction surface. In this study, we used computational fluid dynamics (CFD) to investigate the aerodynamic characteristics induced as a result of the shape and layout of the VG on a multi-MW wind turbine blade. The separated and vortical flow behavior on the suction surface of the wind turbine blade equipped with VGs was captured by the Reynolds-averaged Navier–Stokes (RANS) steady-flow simulation. The parametric sensitivity study of the VG shape parameters such as the chord-wise length, height, and interval of the fair of VGs was conducted using thick DU airfoil on the blade inboard area. Based on these results, the response surface method (RSM) was used to investigate the influence of the design parameters of the VG. Based on the CFD results, the VG design parameters were selected by considering the lift coefficient and vorticity above the trailing edge. The maximum vorticity from the trailing edge of the selected VG and the lift coefficient were 55.7% and 0.42% higher, respectively, than the average. The selected VG design and layout were adopted for a multi-MW wind turbine and reduced stall occurrence in the blade root area, as predicted by the simulation results. The VG improved the aerodynamic performance of the multi-MW wind turbine by 2.8% at the rated wind speed.