Synthesis of catalyst by the organic solvent is an attractive strategy for improving the oxygen vacancy concentration and catalytic activity. Due to the excellent reducibility of ethylene glycol (EG), the reduction strategy was designed to synthesize α-MnO2-EG, and for toluene oxidation. The results showed that EG could significantly increase the oxygen vacancy concentration and catalytic activity of α-MnO2-EG. The oxygen vacancy concentration of α-MnO2-EG-160 is 30% higher than that of α-MnO2-H2O, which leads to the significant low-temperature catalytic performance of the α-MnO2-EG-160 catalyst (T90 = 183 °C), much lower than the currently reported MnO2-based catalysts. The structure–activity relationship of the α-MnO2-EG-160 has been explained. To be specific, EG macromolecules could intrude into [MnO6] framework to exfoliate oxygen atoms and generate oxygen vacancies, which not only improves redox properties, but also promotes the adsorption of toluene. Furthermore, the toluene catalytic mechanism of α-MnO2-EG-160 based on oxygen vacancies was proposed.