This paper investigates a nonlinear output feedback fault-tolerant control method for the hypersonic flight vehicles with non-affine actuator faults. Compared to the existing investigations, with little aerodynamic knowledge, the proposed controller tackles three practical issues simultaneously, including the inaccurate onboard measurements of the flow angles, unknown non-affine actuator faults and actuator saturation. Drawing support from the differentiator technique, an estimation method for the unmeasured flight path angle is devised, and then an available transformed error variable is defined to construct control laws. Tracking differentiators are introduced to establish uncertainty observers for estimating the unknown model functions including the influences caused by the non-affine actuator faults, and tackle the “explosion of terms” inherent in backstepping. Besides, to improve the controller's performance when the actuator saturation happens, a novel anti-windup strategy is developed to settle the problem that many existing anti-windup strategies are not workable if the non-affine actuator faults happen. Finally, comparative simulation results are provided to demonstrate the effectiveness and superiority of the proposed method.