•Coupling COMSOL simulations with acoustic pressure maps informs sono-reactor design.•Simulations show high acoustic pressures along the neck of a multi-stepped horn.•Hydrophone measurements indicate cavitation along horn neck and verify simulations.•Conical bottom reactor maximizes cavitational volume compared to typical reactors. Scaled-up and economically viable sonochemical systems are critical for increased use of ultrasound in environmental and chemical processing applications. In this study, computational simulations and acoustic pressure maps were used to design a larger-scale sono-reactor containing a multi-stepped ultrasonic horn. Simulations in COMSOL Multiphysics showed ultrasonic waves emitted from the horn neck and tip, generating multiple regions of high acoustic pressure. The volume of these regions surrounding the horn neck were larger compared with those below the horn tip. The simulated acoustic field was verified by acoustic pressure contour maps generated from hydrophone measurements in a plexiglass box filled with water. These acoustic pressure contour maps revealed an asymmetric and discrete distribution of acoustic pressure due to acoustic cavitation, wave interaction, and water movement by ultrasonic irradiation. The acoustic pressure contour maps were consistent with simulation results in terms of the effective scale of cavitation zones (∼10cm and <5cm above and below horn tip, respectively). With the mapped acoustic field and identified cavitation location, a cylindrically-shaped sono-reactor with a conical bottom was designed to evaluate the treatment capacity (∼5L) for the multi-stepped horn using COMSOL simulations. In this study, verification of simulation results with experiments demonstrates that coupling of COMSOL simulations with hydrophone measurements is a simple, effective and reliable scientific method to evaluate reactor designs of ultrasonic systems.