This paper demonstrates a novel approach for enhancing ultrasound-induced heating by the introduction of acoustic cavitation using simultaneous sonication with low- and high-frequency ultrasound. A spherical focused transducer (566 or 1155 kHz) was used to generate the thermal lesions, and a low-frequency planar transducer (40 or 28 kHz) was used to enhance the bubble activity. Ex vivo fresh porcine muscles were used as the target of ultrasound ablation. The emitted signals and the signals backscattered from the bubble activity were also recorded during the heating process by a PVDF-type needle hydrophone, and thermocouples were inserted to measure temperatures. Compared with the lesions formed by a single focused transducer, the size of the lesions generated by this approach were as much as 140% larger along the axial direction and 200% larger along the radial direction for combined 566- and 40-kHz sonication. They were 47% and 66% larger along the axial and radial directions, respectively, for combined 1155- and 28-kHz sonication. Cavitation activities enhanced by low-frequency ultrasound were confirmed by the presence of subharmonics in the spectrum and temperature increase as a result of increased tissue absorption. These observations imply that cavitation-enhanced lesions can be generated without reducing the penetration ability; they also show the advantage of producing larger and more uniform thermal lesions by multiple sonications. This technique provides an easy and effective way to achieve cavitation-enhanced heating, and may be useful for generating large and deep-seated thermal lesions.