Strong nonlinearities, uncertainties, and disturbances present great challenges to the control of the dissolved oxygen (DO) in a wastewater treatment process (WWTP). To deal with those undesired issues, in this article, a scalable-bandwidth extended state observer (SESO) is proposed, and the SESO-based adaptive sliding-mode control (ASMC) is designed. By the SESO, the time-varying total disturbance can be estimated more accurately and compensated more effectively. For the disturbances that are not addressed completely, an ASMC is employed to suppress them. Due to the advantages of both SESO and ASMC, the DO can be regulated more desirably. The benchmark simulation model Number 1 is taken to verify the proposed SESO-based ASMC. Comparative simulation results highlight the advantages of the proposed approach.