To improve the reliability of spacecraft system, an active fault tolerant control technique for spacecraft under the influence of disturbance was studied. First, in order to realize fault diagnosis under disturbance and reduce the time delay from fault detection to fault estimation, the concerned faults were extended to state vectors, and an unknown input observer was proposed for the integrated design of fault detection and fault estimation unit. Then, considering that the method needs to be further processed for interference estimation and can only solve the differentiable fault type, a novel adaptive sliding mode unknown input observer was designed, which can ensure the estimation of fault and disturbance decoupling at the same time and deal with a wider range of fault types. Finally, in view of the estimation error of the observer, a multivariable terminal sliding mode fault tolerant controller was proposed to improve its control performance. Simulation results show that the active fault tolerant control technique could realize fault diagnosis under the influence of disturbance and ensure the rapid recovery of control performance.