In this paper, the problems of stabilization and disturbance rejection in the control of class I of underactuated mechanical systems (UMS) are addressed. Based on a global change of coordinates, the original dynamic model is transformed into a strict-feedback form and a Super-Twisting (STW) controller is designed to resolve the stabilization problem. To deal with the problem of uncertainties and external disturbances in UMS, a disturbance observer (DO) is proposed for the estimation of the input disturbances in the aim of compensating them in the controller and improving the performance and robustness of the resulting closed-loop system. Indeed, the proposed observer-based scheme is compared with the standard STW controller. Both controllers have been implemented and validated through real-time experiments on the inertia wheel inverted pendulum. The obtained results show clearly the superiority of the proposed observer-based STW control scheme and its effectiveness in terms of external disturbance rejection.