The global shortage of freshwater and inadequate supply of clean water have necessitated the implementation of robust technologies for wastewater purification, and Fenton-like chemistry is a highly-promising approach. However, realizing the rapid Fenton-like chemistry for high-efficiency degradation of organic micropollutants (OMs) remains challenging. Herein, one novel system was constructed by a Co single-atom catalyst activating peroxymonosulfate (PMS), and the optimal system (SA-Co-NBC-0.2/PMS) achieved unprecedented catalytic performance towards a model OM [Iohexol (IOH)], i.e., almost 100% decay ratio in only 10 min (the observed rate constant: 0.444 min(-1)) with high electrophilic species O-1(2) (singlet oxygen) generation. Theoretical calculations unveiled that Co-N-4 sites preferred to adsorb the terminal-O of PMS (more negative adsorption energy than other O sites: -32.67 kcal/mol), promoting the oxidation of PMS to generate O-1(2). Iodine (I)23 (0.1097), I24 (0.1154) and I25 (0.0898) on IOH with higher f(-) electrophilic values were thus identified as the main attack sites. Furthermore, 16S ribosomal RNA high-throughput sequencing and quantitative structure-activity rela-tionship analysis illustrated the environmentally-benign property of the SA-Co-NBC-0.2 and the tapering ecological risk during IOH degradation process. Significantly, this work comprehensively checked the compe-tence of the SA-Co-NBC-0.2/PMS system for organics abatement in practical wastewater.