In this research, sulfamethoxazole (SMX) degradation was investigated using ultrasound (US), ozone (O3) and ultrasound/ozone oxidation process (UOOP). It was proved that ultrasound significantly enhanced SMX ozonation by assisting ozone in producing more hydroxyl radicals in UOOP. Ultrasound also made the rate constants improve by kinetics analysis. When ultrasound was added to the ozonation process, the reaction rate increased by 6-26% under different pH conditions. Moreover, main intermediates oxidized by US, O3 and UOOP system were identified. Although the main intermediates in ozonation and UOOP were similar, the introduction of ultrasound in UOOP had well improved the cleavage of S-N bond. In this condition SMX become much easier to be attacked, which led to enhanced SMX removal rate in UOOP compared to the other two examined processes. Finally, the SMX degradation pathways were proposed.