Sonochemical processes applied to wastewater treatment have an influence on the behavior of ultrasonic systems. This is especially due to the load characteristic of the sonochemical process itself and the temperature increase caused by internal damping within the converter. Hence, a controlling device is needed to guarantee the operation in resonance and to keep the vibration amplitude constant. This paper presents a digital control system for the operation of weak to strong damped ultrasonic devices and its application for inactivating Escherichia coli in wastewater. In an experimental investigation, the electric data during a sonochemical process to inactivate E. coli in wastewater is taken into account to analyze the efficacy of the treatment process and the reaction of the vibration system to the process. Frequency response measurements depict that the resonance frequency changes with the sonicated medium and the vibration amplitude decreases with driving current. In addition to a common continuous operation of the system, different pulsed modes are investigated. The experiments prove the common dependencies between inactivation and power level or treatment time. Additionally, it is pointed out that the control of the sonochemical device is of utmost importance to guarantee an efficient treatment of water, because fast process changes, especially in pulsed operation modes, need to be controlled to a steady state as fast as possible. Although a water treatment efficiency increase using pulsed modes was not proved, it is shown, that the performance of the control unit is capable of using different driving modes in water treatment.