Peroxymonosulfate (PMS)-based advanced oxidation processes are perceived as a novel strategy for water purification. However, designing an efficient catalyst with a low metal leaching rate remains challenging. Here, under palygorskite (PAL) mediation, 16%-CoCu0.4Fe1.6O4@PAL (16%-CCFO@PAL) was constructed, exhibiting ample oxygen vacancies (VO) and low metal leakage. The VO was confirmed by systematic characterizations and theoretical calculations. The catalyst showed the efficient catalytic capacity for PMS by dual-path (i.e., metal sites and VO) activation. Large amounts of SO4•-, •OH, and 1O2 were produced, greatly destroying bisphenol S (BPS). BPS removal was greater than 99% within 25 min in the 16%-CCFO@PAL/PMS system. At the metal sites, PMS was activated under the synergistic effects of Co(II)/Co(III), Fe(II)/Fe(III), and Cu(I)/Cu(II) pairs and electron transfer. In addition to metal sites, the VO was also an activation center for PMS, which mainly captured the OI atom in [H-OI-OII-SO3]-, donating an electron to OI and promoting SO4•- generation. The interfacial reaction mechanism was explored by in situ tests, and a dual-path activation mechanism was proposed. This work provides a new perspective for VO-assisted PMS activation for water treatment.