Post-ozonation is an important step during advanced water treatment by ozone-biological activated carbon. Post-ozone dosing control in waterworks is directly related to the operation efficiency of post-ozonation and the treated water quality of advanced water treatment. Source water quality is highly affected by the upstream water quality, climate, and weather conditions, as well as sudden pollution accidents. The influential factors of each link in water treatment plant are complicated. Thus, the influent water quality and water flow of post-ozonation change frequently. When the influent water quality and water flow change, how to adjust the ozone dosage in time to ensure ozonation efficiency and restrict bromate formation is a challenge in operation optimization of post-ozonation. A composite control method consisting of disturbance observer (DOB) and model predictive control (MPC) was proposed based on the control objective of CT value (i.e., product of C and T, Cis the concentration of ozone residual in water, T is the contact time of ozone and water) and proportional control of water flow. MPC was employed for the feedback control of ozone dosing. DOB was adopted to estimate the model mismatch and external disturbance of ozonation caused by the change of influent water quality and water flow. The estimated values were applied for the feed-forward control of ozone dosing. Both simulations and experimental results show that compared with MPC feedback control, the proposed DOB-MPC composite control of post-ozone dosing has better control performance and disturbance rejection effect, which can effectively improve the operation efficiency of post-ozonation and the stability of treated water quality of advanced water treatment.