CoFe2O4 magnetic nanoparticles (CoFe2O4 MNPs) were used as heterogeneous catalysts to activate peroxymonosulfate (PMS) for moxifloxacin (MOX) removal in this study. The impacts of initial pH, PMS, catalyst dosage, coexisting ions, and natural organic matter (NOM) were investigated, and the possible degradation pathways of MOX were proposed. The results indicated that efficient degradation of MOX (99.8%) could be achieved in the CoFe2O4/PMS system with the optimum reaction condition (initial pH = 9, CoFe2O4 dosage = 100 mg/L, PMS dosage = 0.25 mM, reaction time = 30 min, and MOX concentration = 5 mg/L). The rule of MOX degradation followed the pseudo-first order kinetic reaction equation (kobs = 0.194 min−1). According to the results of radical scavenging experiments, the contribution of HO• on MOX removal was negligible, and SO4•− played a dominant role in MOX degradation. Five probable MOX degradation pathways were proposed based on the identified fifteen degradation intermediates, including defluorination, decarboxylation, decyclopropyl reaction, transformation of quinolone moieties, oxidation, and cleavage of nitrogen-containing heterocycle. The existence of 5 mM Cl-, HCO3−, and HA posed stronger negative effects on MOX removal. However, the MOX removal efficiency increased with H2PO4- concentration in the first 15 min. The removal efficiency of MOX decreased significantly in the CoFe2O4/PMS system when the catalyst was reused five times. These research conclusions could provide useful information for the practical application of CoFe2O4/PMS system in wastewater treatment of antibiotics.