A decoupling multivariable control system having two degrees of freedom (2-df) is proposed. The system includes controllers for set-point tracking and for disturbance rejection. Synthesis of an inverse-based multi-input and multioutput (MIMO) decoupler makes use of the zero number deficiency in the adjoint matrix of the process. According to this zero number deficiency, pole(s) and zero(s) are thus introduced to the decoupler to modify the open-loop dynamics and preserve the properness. A new method for synthesizing controllers for disturbance rejection is then presented to design the decoupling controller in the main loop. In addition, model-following and feedforward compensators are incorporated to provide Smith-predictor equivalent capability for set-point tracking. On the basis of the decoupled open-loop process, the controllers for set-point tracking and disturbance are designed independently. Stability robustness of the system can be tuned with two measures for decoupling and model reduction. Robustness of the system to both sensor failure and actuator failure is also included. Simulation examples are used to illustrate the proposed design method. Results from the simulation show that this proposed method is effective for the MIMO control.