Nanobubble (NB) technology has demonstrated the potential to enhance or substitute for current treatment processes in various areas. However, research employing it as a novel advanced oxidation process has thus far been relatively limited. Herein, we focused on the oxidative capacity of oxygen NBs and investigated the feasibility of utilizing their enhanced oxidation of ferrous ions (Fe2+) in a sulfuric acid medium when using copper as a catalyst and their effect mechanism. It was demonstrated that oxygen NBs could collapse to produce hydroxyl radicals (·OH) in the absence of dynamic stimuli using electron spin resonance spectroscopy, and methylene blue was used as a molecular probe for ·OH to illustrate that NB stability, determined by their properties, is the critical factor affecting ·OH release. In subsequent Fe2+ oxidation experiments, it was discovered that both strong acidity and copper ions (Cu2+) contribute to accelerating the collapse of NBs to produce ·OH. While ·OH derived from the collapse of NBs acts on Fe2+, the molecular oxygen generated homologously with ·OH will further activate the catalytic oxidation of Fe2+ by interacting with Cu2+. With the synergistic effect of the above two oxidation-driven mechanisms, the oxidation rate of Fe2+ can be significantly increased up to 88% due to the exceptional properties of oxygen NBs, which facilitate the formation of an atmosphere with persistent oxygen supersaturation and the generation of oxidation radicals. This study provides significant insight into applying NBs as a prospective technology for enhanced oxidation processes.