Pneumatic artificial muscle (PAM), featuring good flexibility and safety, has been widely used in rehabilitation and bionic robots. However, the complex hysteretic nonlinearities and uncertainties of the PAM cause great difficulties and challenges to the accurate modeling and controller design, especially when confronted with unknown external disturbances in applications. This paper proposes a robust control strategy with disturbance compensation for the hysteresis compensation and trajectory tracking of PAMs. Considering the high hysteretic nonlinearity of the PAM, a modified Prandtl-Ishlinskii model is used as a feedforward hysteresis compensator. For the linearized system, adaptive set-membership filtering (ASMF) is used to estimate the nonlinear terms and external disturbances of the overall system. A sliding mode controller (SMC) with disturbance compensation is designed and cascaded to the feedforward hysteresis compensator in series. The stability of the closed-loop system is theoretically proved. The proposed method guarantees that the tracking error of the PAM system is bounded. Finally, the effectiveness and robustness of the proposed controller are verified via a series of experiments on an in-house built testbench for PAMs. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Note to Practitioners</i> —With the increasing demand on human-robot interaction, the safety and compliance of robots have become one key requirement. PAM is a compliant actuator, exhibiting good flexibility, safety, and clean energy. PAM is widely used in rehabilitation robots, whereas its strong hysteresis nonlinearity and sensitivity to external disturbances affect its motion accuracy. This paper proposes an ASMF-based discrete SMC, which uses an inverse hysteresis model to compensate for the strong hysteresis of the PAM and uses ASMF to estimate the lumped disturbance of the system. Compared with the other filters, ASMF is unique in that its estimation error is bounded, which is very useful in the stability proof of the overall system. The effectiveness of the proposed controller is experimentally verified. Experimental results show that PAM’s hysteresis can be efficiently compensated, and the influence of external disturbances can be attenuated by the proposed controller, resulting in improved motion accuracy and robustness. In future work, efforts will be directed towards the modeling and control of PAMs in multi-DOF robots.