In this study, pulsed electric field (PEF)-activated peroxymonosulfate (PMS) (PEF/PMS) was used to degrade ciprofloxacin (CIP) in water. The PEF reduced the polarization effect and the formation of an ion hydration layer compared to the constant electric field (CEF), which more easily promoted the production of active radicals. This study found that the optimal reaction conditions included a PMS concentration of 0.5 g L-1, a pulse power supply voltage of 7 V, a duty cycle of the pulse power supply of 50%, a pulse frequency (f) of 3000 Hz, pH of 3, and an electrode spacing of 3.5 cm. The predicted response value was verified, and the CIP degradation rate was found to be 72.26%, which was consistent with the predicted value. The effect of different reaction systems on the degradation rate of CIP followed the order PEF/PMS > PEF > CEF/PMS > CEF > PMS. The quenching experiments and electron paramagnetic resonance (EPR) analysis showed that hydroxyl radicals ((OH)-O-center dot) were present during CEF oxidation; while in the PEF/PMS system, sulfate radicals (SO4 center dot-) and center dot OH were present. The generation of SO4 center dot- and (OH)-O-center dot was significantly greater in the PEF/PMS system than in the CEF/PMS system. Additionally, 10 kinds of intermediate products were detected during degradation by destroying the piperazine structure of CIP, determined by high-performance liquid chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS). Most of the degradation products are less toxic than CIP, but a few degradation products become more toxic.