An adaptive fuzzy fault-tolerant tracking controller is developed for Near-Space Vehicles (NSVs) suffering from quickly varying uncertainties and actuator faults. For the purpose of estimating and compensating the mismatched external disturbances and modeling errors, a second-order sliding mode disturbance observer (SOSMDO) is constructed. By introducing the norm estimation approach, the negative effects of the quickly varying multiple matched disturbances can be handled. Meanwhile, a hierarchical fuzzy system (HFS) is employed to approximate and compensate the unknown nonlinearities. Several performance functions are introduced and the original system is transformed into one incorporating the desired performance criteria. Then, an adaptive fuzzy tracking control structure is established for the transformed system, and the predefined transient tracking performance can be guaranteed. The rigorous stability of the closed-loop system is proved by using the Lyapunov method. Finally, simulation results are presented to illustrate the effectiveness of the proposed control scheme.