This study investigates the catalytic oxidation of acetone by different crystal phases of MnO2 prepared via different methods. Compared with β-MnO2 and γ-MnO2, α-MnO2 exhibited superior catalytic activity. Moreover, as replacements for traditional hydrothermal methods and air calcination, the use of microwave hydrothermal methods and N2 calcination significantly enhanced the catalytic performance of the MnO2 catalyst. The optimal catalyst, MnO2-WN (α-MnO2 synthesized via microwave hydrothermal method and N2 calcination), converted 100% of 100 ppm acetone below 150 °C, with the CO2 yields reaching 100%. Further, the stability of the catalyst and its potential for other volatile organic compounds (VOCs) were also determined. The experimental data demonstrated that its outstanding activity primarily stemmed from the improved preparation method, enhancing the specific surface area of the catalyst, optimizing the pore structure, improving the redox performance, and generating more acidic sites and active oxygen species, thereby creating a synergistic effect. Finally, the reaction pathway of acetone oxidation on the catalyst surface has been explored. This work provides a new perspective for developing economically efficient MnOx catalysts for removing VOCs.