This paper examines for the first time the combined use of ferrate(VI) (Fe(VI)O4(2-), Fe(VI)) with peroxymonosulfate (PMS) to oxidize four fluoroquinolones (FQs) (flumequine (FLU), enrofloxacin (ENR), marbofloxacin (MAR), and ofloxacin (OFL)) at pH 7.0 and 25.0 °C. The results demonstrate that a combination of PMS and Fe(VI) synergistically enhance removal of FQs compared to the removal seen with either PMS or Fe(VI) alone. The oxidized products (OPs) of the reaction of FLU with the PMS-Fe(VI) system, identified by liquid chromatography high-resolution mass spectrometry (LC-HRMS) techniques, showed transformation products resulted from hydroxylation, ring cleavage, and de-fluorination processes. Thus, the combination of PMS and Fe(VI) can be developed as an innovative oxidative technology to remove contaminants from water.