A trajectory tracking method based on sliding mode control (SMC) and disturbance observer is proposed for the wheeled mobile robot (WMR) suffering from unknown disturbances. First of all, a continuous sliding mode control (CSMC) method is designed for an uncertain WMR. However, when the system confronts stronger disturbances from internal or external, the large control needs to be designed, which will lead to a large steadystate tracking error. To improve robustness and reduce the tracking error, two nonlinear disturbance observers (NDOs) are designed to respectively estimate various unpredictable disturbances in the kinematics and dynamics descriptions of the system studied, such as skiddings, slippings, and parameter uncertainties. Then, with the aid of disturbance estimations, a new trajectory tracking method is constructed for the WMR, which consists of the CSMC and NDOB. What’s more, the stability of the entire closed-loop system under the present control strategy is proved in detail. Finally, the tracking performance of the proposed controller is verified by the simulation.