This paper reports the experimental study on the enhanced cavitation yield via dual-frequency ultrasonic sonication and the multi-frequency single-bubble cavitation bubble modeling. The cavitation yield was characterized using the PCD (passive cavitation detection) method. A dual-frequency (1.5 MHz/3 MHz) pulse ultrasound was used in the tests. It was found that the sonication of dual-frequency ultrasound can produce a significant increase in cavitation yield compared with single-frequency irradiation. The possible mechanisms of the enhanced effect were explained by the single-bubble cavitation model, where the calculated radiated pressure generated by acoustic bubble cavitation was found greater in dual-frequency cases. The findings from this paper are promising for the design of multi-frequency ultrasound system with enhanced cavitation for a number of biomedical, biological and chemical processing applications.