Commercial nanosized zero-valent copper (nZVC) was used as hydrogen peroxide (H2O2) activator in conjunction with ultrasonic irradiation (US) for the oxidative degradation of norfloxacin (NOR) in this study. Compared with silent degradation system, a significantly enhanced NOR removal was obtained in sono-advanced Fenton process, which involved a synergistic effect between sonolysis and Fenton-like reaction. Almost complete removal of NOR was achieved at 30min when the operating conditions were 0.25g/L nZVC and 10mM H2O2 with ultrasound power of 240W at 20kHz. The released Cu+ during the nZVC dissolution was the predominant copper species to activate H2O2 and yield hydroxyl radicals (OH) in US/nZVC/H2O2 system. According to the radical quenching experiments and electron paramagnetic resonance technique, hydroxyl radicals in solution (OHfree) were verified as the primary reactive species, and superoxide anion radicals (O2-) were regarded as the mediator for the copper cycling by reduction of Cu2+ to Cu+. NOR removal efficiencies were improved in various degrees when increased nZVC dosage, ultrasound power, hydrogen-ion amount and H2O2 concentration. Moreover, the inhibitory effect of different inorganic salts on NOR degradation followed the sequence of Na2SO4>NaNO3≈no salt>NaCl>NaHCO3. Finally, eleven intermediates were identified and five oxidation pathways were proposed, the cleavage of piperazine ring and transformation of quinolone group seemed to be the major pathway.