In order to solve the trajectory tracking problem of mobile robot with centroid deviation under nonholonomic constraints, a trajectory tracking control method for mobile robot with improved sliding mode variable structure is proposed. The tracking controller with global asymptotic stability was also obtained by this method. Based on the motion model of threewheeled mobile robot, and the tracking controller design was divided into two parts. In the first part, using X direction and forward direction with virtual feedback variable, the stability of the control system was analyzed by Lyapunov method, and the switching function was designed. The second part, the sliding mode controller was designed, which adopts exponential approach law and uses S type exponential function instead of symbol function. Then the jitter of the sliding mode variable structure control was reduced. Then, the control law of linear velocity and angular velocity was designed to asymptotically stabilize the tracking error of mobile robot and to realize the global asymptotic tracking of the reference trajectory. The experimental results show that the control law can be stable in a very short time, and the tracking plane coordinate error and forward angle error can converge to zero in a very short time. Moreover, the mobile robot can track the desired trajectory effectively, and its control effect is obviously improved, and the method has good antijamming performance.