In wastewater treatment processes, the concentration of dissolved oxygen affects the performance of wastewater treatment directly. It is one of the key factors that determines effluent quality of the wastewater treatment. However, a simple closed-loop control has a high-energy consumption, and it cannot guarantee the effluent quality due to large perturbations in wastewater treatment plants, such as the influent rate, the temperature, and the complex biochemical reactions. In this paper, a new disturbance rejection controller is designed to address those perturbations. Dynamics of dissolved oxygen is transformed into a controllable canonical form. Discrepancy between the dissolved oxygen dynamics and the controllable canonical form is estimated by a disturbance observer and compensated by a control law. Stability and the bound of tracking errors are obtained. Finally, numerical results on the benchmark simulation model number 1 are presented to confirm the proposed method.