Modulating the coordination environments and the electronic configurations of the metal centers of single-atom catalysts (SACs) to further improve the activation of peroxomonosulfate (PMS) remains a great challenge. In this work, oxygen (O) atoms were doped into Fe-N4 single-atom catalysts via oxygen-containing acid precursors to adjust the electronic structure to enhance PMS activation. The prepared Fe-N4O single-atom catalysts exhibited excellent oxidation capacity, tolerance, elevated stability and continuous organic oxidation. The primary degradation pathway is the high-valent iron (Fe IV = O) and the electron transfer mechanism. DFT calculations indicated that the adsorption energy and electron transfer number of second-shell-coordinated Fe-N4O were much higher than those of one-shell-coordinated Fe-N3O. The introduction of O atoms increased the electron density of the central Fe atoms and the electron delocalization domains, which increased the electron transfer capacity. This research provides a method to finely control the coordination environment and electronic structure of Fe-N4, revealing the unique dynamic regulation mechanism of heteroatoms for advanced oxidation, and providing a reference for the design of high-efficiency Fenton-like-based catalysts.