Fenton reaction has important implications in biology- and environment-related remediation. Hydroxyl radicals (OH) and hydroxide (OH) were formed by a reaction between Fe(II) and hydrogen peroxide (HO). The acidic HO/Fe(II/III) redox-induced low HO utilization efficiency is the bottleneck of Fenton reaction. Electron paramagnetic resonance, surface-enhanced Raman scattering, and density functional theory calculation indicate that the unpaired electrons in the defects of carbon quantum dots (CQDs) and the carboxylic groups at the edge have a synergistic effect on CQDs Fenton-like catalysis. This leads to a 33-fold higher HO utilization efficiency in comparison with Fe(II)/HO Fenton reaction, and the pseudo-first-order reaction rate constant () increases 38-fold that of Fe(III)/HO under equivalent conditions. The replacement of acidic HO/Fe(II/III) redox with CQD-mediated Fe(II/III) redox improves the sluggish Fe(II) generation. Highly effective production of OH in CQDs-Fe(III)/HO dramatically decreases the selectivity of toxic intermediate benzoquinone. The inorganic ions and dissolved organic matter (DOM) in real groundwater show negligible effects on the CQDs Fenton-like catalysis process. This work presents a process with a higher efficiency of utilization of HO chemical oxidation (ISCO) to remove persistent organic pollutants.