Effect of second-harmonic superimposition on cavitation and sonochemical reaction was investigated in a propagation mode by using a plane wave transducer piezoelectrically active at both fundamental and second-harmonic frequencies. The rate of iodine release induced by ultrasound at 1 MHz with a superimposed wave at 2 MHz showed significant dependence on the phase relation between the two waves. The largest rate was obtained at the relative phase which maximizes the magnitude of negative peak pressure while almost no iodine release was observed at the relative phase which maximizes the magnitude of positive peak pressure. At this optimum relative phase, the dependence of iodine release and subharmonic emission on the ultrasound power at 1 MHz and 2 MHz was studied. The results clearly show the synergistic effects of the fundamental and second harmonic on the chemical reaction and on higher-order subharmonic emission which typically accompanies acoustic cavitation.