A novel sonophotochemical Fenton-like system was investigated in this study for degradation of antibiotic sulfamethazine (SMZ). In the presence of oxalic acid (Ox), the heterogeneous Fe3O4-catalyzed system (US/UV/Fe3O4/Ox) could induce in-situ generation of H2O2 and also Fenton-like reaction. A Significant synergistic SMZ degradation including significantly enhanced SMZ mineralization and detoxification was achieved in the system, as compared to its corresponding individual systems. Ultrasound (US) treatment could eliminate the initial lag period of SMZ degradation which appeared in UV/Fe3O4/Ox system without the pre-dissolution phase. This phenomenon was evidenced by significant enhancements in the initial dissolution rate of the iron oxides as well as production rate of the reactive oxygen species (ROS). A reaction mechanism involving a heterogeneous/homogenous iron cycle and a series of homogenous radical reactions was proposed. The promotional role of US could be mostly ascribed to the sonochemcial cavitation effect in both heterogeneous solid-liquid interphase reactions and homogenous radical reactions. The cleavage of S-N bond via center dot OH attack would be the main SMZ decomposition pathway. The solution pH and [Fe3O4:Ox] ratio were the two important factors for SMZ degradation. The repeating SMZ degradation tests of the US/UV/Fe3O4/Ox system also suggested that Fe3O4 was a favorable catalyst for application of the system in wastewater treatment. (C) 2014 Elsevier B.V. All rights reserved.