We investigated the effect of second-harmonic superimposition (SHS) on the oxidation of iodide ions induced by ultrasound with two frequency components : 10.3 and 2.06 MHz. With SHS, the oxidation rate reached a maximum when the acoustic intensity ratio of the fundamental to the second harmonic was about 1:1, while conventional single-frequency exposure at either one of the two frequencies did not induce oxidation even at an acoustic intensity 10 times the threshold for SHS. The rate of oxidation strongly depended on the phase of the second harmonic relative to the fundamental. The reaction was observed only at the second-harmonic phase ranging from maximizing the peak rarefaction to maximizing the rarefaction increasing rate. Simultaneously measured subharmonic emission, an indicator of cavitation, suggested that the effect of SHS on sonochemical reaction is due to its ability to induce cavitation efficiently.