This paper presents a comprehensive study of the evaluation of the effect of spar cap fiber orientation angle of composite blades with induced bending–torsion coupling (IBTC) on the aero-structural performance wind turbines. Aero-structural performance of wind turbines with IBTC blades is evaluated with the fatigue load mitigation in the whole wind turbine system, tower clearances, peak stresses in the blades, and power generation of wind turbines. For this purpose, a full E-glass/epoxy reference blade has been designed, following the inverse design methodology for a 5-MW wind turbine. An E-glass/epoxy blade with IBTC and novel, hybrid E-glass/carbon/epoxy blades with IBTC have been designed and aeroelastic time-marching multibody simulations of the 5-MW turbine systems, with the reference blade and the blades with IBTC, have been carried out using six different randomly generated turbulent wind profiles. Fatigue-equivalent loads (FELs) in the wind turbine have been determined as an average of the results obtained from the time response of six different simulations. The results reveal that certain hybrid blade designs with IBTC are more effective in fatigue load mitigation than the E-glass–epoxy blade with IBTC, and besides the fiber orientation angle, sectional properties of hybrid blades must be adjusted accordingly using proper number of carbon/epoxy layers in the sections of the blade with IBTC, in order to simultaneously reduce generator power losses and the FEL.