The advanced manufacture technology requires that multi-axis coordinated motion computer numerical control (CNC) machine tools have the capability of high smoothness and high precision. At present, the study of the motion smoothness mainly concentrates on the acceleration and deceleration control method and the look-ahead process of velocity planning in the interpolation stage. The control strategy of the contouring error mainly focuses on tracking error control, cross-coupling control, and optimal control. In order to improve the motion smoothness and contouring precision for multi-axis high-speed CNC machine tools, a multi-axis modified generalized predictive control approach was presented in this paper. In the control strategy, the estimation models of tracking error, contouring error, velocity error, and acceleration error were structured separately. A new improved quadratic performance index was proposed to guarantee the minimum of these errors. Generalize predictive control was also introduced, a multi-axis generalized predictive control model was deduced for motion smoothness and machining precision for multi-axis coordinated motion CNC system, and an approved multi-axis generalized predictive controller based on the model was designed in this paper. The proposed predicted control approach was evaluated by simulation and experiment of circular, noncircular, and space line trajectories, respectively. These simulative and experimental results demonstrated that the proposed control strategy can significantly improve the motion smoothness and contouring precision. Therefore, the new position control method can be used for the servo control system of multi-axis coordinated motion CNC system, which increases motion smoothness and machining precision of CNC machine tools.