The chemical stability of anion polymer electrolyte membranes (AEMs) determines the durability of an AEM water electrolyzer (AEMWE). The alkaline stability of AEMs has been widely investigated in the literature. However, the degradation of AEM at neutral pH closer to the practical AEMWE operating condition is neglected, and the degradation mechanism remains unclear. This paper investigated the stability of quaternized poly(p-phenylene oxide) (QPPO)-based AEMs under different conditions, including Fenton solution, H2O2solution and DI water. The pristine PPO and chloromethylated PPO (ClPPO) showed good chemical stability in the Fenton solution, and only limited weight loss was observed, 2.8% and 1.6%, respectively. QPPO suffered a high mass loss (29%). Besides, QPPO with higher IEC showed a higher mass loss. QPPO-1 (1.7 mmol g−1) lost nearly twice as much mass as QPPO-2 (1.3 mmol g−1). A strong correlation between the degradation rate of IEC and H2O2concentration was obtained, which implied that the reaction order is above 1. A long-term oxidative stability test at pH neutral condition was also conducted by immersing the membrane in DI at 60 °C water for 10 months. The membrane breaks into pieces after the degradation test. The possible degradation mechanism is that oxygen or OH˙ radicals attack the methyl group on the rearranged ylide, forming aldehyde or carboxyl attached to the CH2group.