In this study, the Fe clusters were anchored onto 2D porous g-C3N4 nanosheets to synthesize Photo-Fenton catalysts Fe-CNS with highly and uniformly dispersed Fe-Nx active sites via a supramolecular thermal polymerization and subsequent impregnation strategy. The obtained Fe-CNS composites exhibited excellent Photo-Fenton catalytic activity and stability even under high pH and anion conditions, suggesting Fe clusters doping into 2D porous g-C3N4 nanosheets host through Fe-Nx coordination structures enhanced the separation efficiency of light-generated charge carriers, promoted Fe3+/Fe2+ redox cycle, accelerated the activation of H2O2 and improved the stability of Fe species and leading to a remarkable Photo-Fenton synergistic effect. Among these Fe-CNS composites, Fe-CNS with doping amount of 7 % Fe species shows superior Photo-Fenton activity for the elimination of Tetracycline (TC), and the corresponding k value is 0.04729 min−1, which is 25.4 times superior to that of photocatalytic oxidation TC of bulk g-C3N4, indicating that the strategy on changing Fe doping amount yielded opportunity to optimize Photo-Fenton combined action between Fe clusters and g-C3N4 nanosheets host. The degradation mechanism of TC using Fe-CNS composites in the Photo-Fenton system has been further elucidated by considering that the embedded Fe clusters in the N-rich 2D g-C3N4 nanosheets form abundant Fe-Nx active sites.