Magnetic CuFe2O4 nanoparticles were successfully synthesized with a coprecipitation method at 500 °C calcination temperature, and were utilized to degrade levofloxacin (LEV) as a peroxymonosulfate (PMS) activator. The structure and composition of the nanocatalyst were characterized by a series of methods, including scanning electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, vibrating sample magnetometer and thermogravimetric analysis. The effects of the PMS concentration, the catalyst dosage, the LEV initial concentration, the pH value and the inorganic anions on the LEV degradation were also explored. The results revealed that the designed CuFe2O4/PMS system had high activity and excellent stability in the complex conditions. The degradation efficiency of LEV still reached above 80% after four recycles of CuFe2O4 catalyst. The reactive species quenching experiments and electron paramagnetic resonance analysis suggested the existence of superoxide radicals, single oxygen, hydroxy radicals and sulfate radicals, and the first two were dominant radical oxygen species. Based on the mechanism analyses, the efficient degradation of LEV was probably due to the continuous generation of reactive species under the condition of Fe(III)/Fe(II) and Cu(II)/Cu(I) redox cycles. The research provided a reasonable reference for the PMS activation mechanism-based spinel-type ferrite catalysis.