Acoustic cavitation has been utilized in many industrial applications to enhance the process intensity. To obtain the most energy-efficient sonochemical activity, the excitation signal specifications are of great importance. This investigation focuses on the effect of different wave characteristics on sonochemical activity including erosion rate and measured sound pressure levels below the surface and beside the high power sonotrode. Signal characteristics as frequency bandwidth, sweep rate, and direction are considered aspects of time signal shape transformation. Altogether eight groups of factors were evaluated in a two-level and replicated design. Numerical simulation has been conducted to achieve the optimized geometrical design and to prevent parasitic modes in sonotrode’s configuration. Results show that negative direction with 100 ms sweep rate and 800 Hz frequency bandwidth generates both the highest sound pressure level and erosion rate. The findings from this study are aimed to be implemented in an energy-efficient flow through sonochemical reactor design.