The frequent detection of antibiotics in water bodies gives rise to concerns about their removal technology. In this study, the degradation kinetics and mechanisms of norfloxacin (NOR), a typical fluoroquinolone pharmaceutical, by the UV/peroxydisulfate (PDS) was investigated. NOR could be degraded effectively using this process, and the degradation rate increased with the increasing dosage of PDS but decreased with the increasing concentration of NOR. In real water, the degradation of NOR was slower than that in ultrapure water, which indicated that laboratory results cannot be directly used to predict the natural fate of antibiotics. Further experiments suggested that the degradation of NOR was the most fast under neutral condition, the existence of HA or FA inhibited the degradation of NOR, and the presence of inorganic ions (NO3−, Cl−, CO32− and HCO3−) had no significant effect on degradation of NOR. Total organic carbon (TOC) removal rate (40%) indicated NOR was not completely mineralized, and six transformation products were identified, and possible degradation pathways of NOR had been proposed. It can be prospected that UV/PDS technology could be used for advanced treatment of wastewater containing fluoroquinolones.