The lower limb exoskeleton can improve mobility and safety during rehabilitation for human. However, most current exoskeleton systems are not capable of providing variable joint stiffness in response to changing external demands. In this paper, a knee exoskeleton based on the series elastic actuator (SEA) is designed for safe human-computer interaction. The structural dimensions of the exoskeleton actuation mechanism were optimized based on gait biomechanics to ensure stability and compactness. While maintaining the mechanism range of motion (ROM), this optimization ensures that less peak force is required during the gait cycle. However, the insertion of series elastic actuators inevitably brings new challenges for high precision control of the exoskeleton, such as the problems of modeling errors, compliance, friction, and external disturbances in the exoskeleton joint. To achieve high precision control of the exoskeleton, an extended disturbance observer (EDO) based command filtered backstepping control (CFBC) of the knee exoskeleton is developed. The effective observation of friction, external disturbances, and modeling errors in the system is obtained by the EDO. Compared with conventional backstepping control, the CFBC can not only solve the “explosion of complexity” problem through a command filter but also reduce filter errors by an error compensation mechanism. Based on the Lyapunov stability, all signals in the closed-loop system are semiglobal uniformly ultimately bounded. Finally, comparison simulation results demonstrate the effectiveness of the proposed control approach.