The problem of tracking dissolved oxygen is one of the most complex and fundamental issues related to biological processes. The dissolved oxygen level in aerobic tanks has a significant influence on the behavior and activity of microorganisms. Aerated tanks are supplied with air from an aeration system (blowers, pipes, throttling valves, and diffusers). It is a complex, dynamic system governed by nonlinear hybrid dynamics. Control of the aeration system is also difficult in terms of control of the dissolved oxygen. In this article, a two-level multivariable control system for tracking dissolved oxygen and controlling an aeration system is designed. A nonlinear model predictive control algorithm was applied to design controllers for each level. This overall hierarchical control system was validated by simulation based on real data records provided by a water resource recovery facility located in Kartuzy, Northern Poland. The effect of control system parameters and disturbances was also investigated.