Novel copper-nickel ferrite nanocatalyst loaded on multi-walled carbon nanotube (MWCNTs-CuNiFe2O4) was synthesized and applied to activate peroxymonosulfate (PMS) in the degradation of the reactive black 5 (RB5). The structure of the catalyst was well characterized by scanning electron microscope (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray powder diffraction (XRD). The MWCNTs-CuNiFe2O4/PMS system showed a high performance in the degradation of RB5 with a kinetic rate of 1.5–2.5 times higher than homogeneous and heterogeneous systems. Maximum degradation efficiency (99.60%) was obtained at an initial pH of 7, catalyst dosage of 250 mg/L, PMS dosage of 4 mM, the temperature of 25 °C, and reaction time of 15 min. Anion experiments emphasized that the presence of nitrate, carbonate, and phosphate in the solution reduced the degradation efficiency by producing reactive species with low oxidation potential. The RB5 degradation rate evolved with temperature, and the activation energy was obtained to be 44.48 kJ/mol. The mechanism of PMS activation and production of free radicals was proposed based on tert-butyl alcohol (TBA), ethanol (EtOH), and potassium iodide (KI) scavengers. Trapping experiments showed that both sulfate (SO4 •- ) and hydroxyl (• OH) radicals are involved in the catalytic degradation of RB5. The effective treatment of real wastewater and tap water by the MWCNTs-CuNiFe2O4/ PMS system requires a long reaction time. Gas chromatography-mass spectrometry (GC-MS) analysis indicated that RB5 can be degraded via methylation, decarboxylation, hydroxylation, and ring/chain cleavage pathways. The stable catalytic activity after three consecutive cycles suggested that MWCNTs-CuFe2O4 is a novel reusability catalyst in PMS activation.