We develop a novel disturbance observer-based adaptive fuzzy control approach in this paper for a class of uncertain multi-input-multi-output mechanical systems possessing unknown input nonlinearities, i.e., deadzone and saturation and time-varying external disturbance. It is shown that the input nonlinearities can be represented by a nominal part and a nonlinear disturbance term. High-dimensional integral-type Lyapunov function is used to construct the controller. Fuzzy logic system is employed to cancel model uncertainties, and disturbance observer is also integrated into control design to compensate the fuzzy approximation error, external disturbance, and nonlinear disturbance caused by the unknown input nonlinearities. Semiglobally uniformly ultimately boundness of the closed-loop control system is guaranteed with tracking errors keeping bounded. Experimental studies on a robotic exoskeleton using the proposed control demonstrate the effectiveness of the approach.