As an efficient active oxidant for the selective degradation of pollutants in wastewater, the high-valent copper species Cu(III) with persulfate activation has attracted substantial attention in some Cu-based catalysts. However, the systematic study of a catalyst structure and mechanism about Cu(III) with peroxydisulfate (PDS) activation is challenging owing to the coexistence of multiple Cu species and the structural symmetry of PDS. Herein, we anchored a Cu atom with two pyridinic N atoms to synthesize a single-atom Cu catalyst (Cu SA -NC). Experimental characterizations and theoretical calculations complemented each other well because of the uniform atomic active sites. The single-atom Cu was identified as the active site, and the unsaturated Cu-N 2 configuration was more conductive to PDS activation than the saturated Cu-N 4 configuration. Benefiting from the generation of Cu(III), Cu SA -NC exhibited an obvious selective and anti-interference performance for pollutant degradation in a complex matrix. The superior catalytic activity of Cu SA -NC compared with that of other reported Cu-based catalysts and good durability in a continuous-flow experiment further revealed the potential of Cu SA -NC for practical applications. This work strongly deepens the understanding of the generation of Cu(III) in a single-atom Cu catalyst with unsaturated Cu-N 2 sites under PDS activation and develops an efficient approach for actual water purification.