This paper proposes an adaptive fault‐tolerant control (FTC) method for hypersonic vehicle (HSV) with unexpected centroid shift, actuator fault, time‐varying full state constraints, and input saturation. The occurrence of unexpected centroid shift has three main effects on the HSV system, which are system uncertainties, eccentric moments, and variation of input matrix. In order to ensure the time‐varying state constraints, a novel attitude state constraint control strategy, to keep the safe flight of HSV, is technically proposed by a time‐varying state constraint function (TVSCF). A unified controller is designed to handle the time‐varying state constraints according to the proposed TVSCF. Then, the constrained HSV system can be transformed into a novel free‐constrained system based on the TVSCF. For the variation of system input matrix, input saturation and actuator fault, a special Nussbaum‐type function is designed to compensate for those time‐varying nonlinear terms. Additionally, the auxiliary systems is designed to compensate the constraint of system control inputs. Then, it is proved that the proposed control scheme can guarantee the boundedness of all closed‐loop signals based on the Lyapunov stability theory. At last, the simulation results are provided to demonstrate the effectiveness of the proposed fault‐tolerant control scheme.