The effect of ultrasound irradiation on molybdenum trioxide has been investigated. Under ultrasonic irradiation, spherical-like MoO3 nanoparticles were obtained, while bulk-like MoO3 nanoparticles were prepared without ultrasonic irradiation. The changes in the physicochemical properties of MoO3 have been investigated using techniques such as X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM) and ultraviolet and visible spectroscopy (UV-vis). The physicochemical changes of MoO3 due to ultrasound irradiation have been attributed to the sonochemical cavity collapse onto the molybdenum trioxide particles. The ultrasonically prepared particles can also greatly improve the photochromism efficiency.