The assimilation of antibiotic resistance genes (ARGs) by pathogenic bacteria poses a severe threat to public health. Here, we reported a dual-reaction-site–modified Co SA /Ti 3 C 2 T x (single cobalt atoms immobilized on Ti 3 C 2 T x MXene) for effectively deactivating extracellular ARGs via peroxymonosulfate (PMS) activation. The enhanced removal of ARGs was attributed to the synergistic effect of adsorption (Ti sites) and degradation (Co-O 3 sites). The Ti sites on Co SA /Ti 3 C 2 T x nanosheets bound with PO 4 3− on the phosphate skeletons of ARGs via Ti–O–P coordination interactions, achieving excellent adsorption capacity (10.21 × 10 10 copies mg −1 ) for tetA, and the Co–O 3 sites activated PMS into surface-bond hydroxyl radicals (•OH surface ), which can quickly attack the backbones and bases of the adsorbed ARGs, resulting in the efficient in situ degradation of ARGs into inactive small molecular organics and NO 3 . This dual-reaction-site Fenton-like system exhibited ultrahigh extracellular ARG degradation rate (k > 0.9 min −1 ) and showed the potential for practical wastewater treatment in a membrane filtration process, which provided insights for extracellular ARG removal via catalysts design.