The efficient activation and selective high-valent metal-oxo (HVMO) species generation remain challenging for peroxymonosulfate (PMS)-based advanced oxidation processes (PMS-AOPs) in water purification. The underlying mechanism of the activation pathway is ambiguous, leading to a massive dilemma in the control and regulation of HVMO species generation. Herein, bioinspired by the bio-oxidase structure of cytochrome P450, the axial coordination strategy was adopted to tailor a single-atom cobalt catalyst (CoN4S-CB) with an axial S coordination. CoN4S-CB high-selectively generated high-valent Co-Oxo species (Co(IV)=O) via PMS activation. Co(IV)=O demonstrated an ingenious oxygen atom transfer (OAT) reaction to achieve the efficient degradation of sulfamethoxazole (SMX), and this allowed robust operation in various complex environments. The axial S coordination modulated the 3d orbital electron distribution of the Co atom. Density functional theory (DFT) calculation revealed that the axial S coordination decreased the energy barrier for PMS desorption and lowered the free energy change (ΔG) for Co(IV)=O generation. CoN4S-PMS* had a narrow d-band close to the Fermi level, which enhanced charge transfer to accelerate the cleavage of O-O and O-H bonds in PMS. This work provides a broader perspective on the activator design with natural enzyme structure-like active sites to efficient activate PMS for selective HVMO species generation.