A nonlinear disturbance observer-based control scheme is proposed for the trajectory tracking of a class of underactuated systems. Firstly, a tracking error-based output function is proposed and the equation transformation and Butterworth low-pass filter are applied to solve the problem of unknown control directions. By introducing a novel nonlinear disturbance observer, which is used to compensate for unknown system model, the need to know the structure of the system and its parameters is obviated. The internal and external dynamics are rigorously analyzed, thereby proving the uniform ultimate boundedness of the error trajectory. Finally, the proposed method is applied to the cart-pole inverted pendulum, and the simulation results show its effectiveness.