In recent years, robot manipulator arms have become increasingly prevalent and are playing pivotal roles across various industries. Their ability to replace human labor in arduous and hazardous tasks has positioned them as indispensable assets. Consequently, there has been a surge in research efforts aimed at enhancing their operational performance. The imperative to improve their efficiency and effectiveness has garnered significant attention within the research community. In this study, a novel fault-tolerant control (FTC) scheme for robot manipulators to handle the effects of the unknown input is proposed to aid robots in achieving good tracking performance. In the first step, an extended state observer (ESO) is constructed to approximate both velocities and the unknown input in the robot system. The observer offers estimation information with good accuracy and quick convergence. The estimated signals are then combined with computed torque control (CTC), which is a useful control technique for trajectory tracking of robot manipulator systems, to construct an active FTC to decrease the influences of the unknown input. The proposed algorithm does not require velocity measurement in the design process. In addition, with a novel design approach, the combination of controller and observer provides a novel control signal that delivers higher tracking performance compared to the traditional design approach. The global and asymptotic stability of the suggested technique is proved through the Lyapunov theory. Finally, simulations are implemented on a 2-degree-of-freedom (DOF) robot manipulator to validate the efficiency of the proposed controller–observer method.