Alkaline fuel cells (AFCs) with an anion exchange membrane (AEM) electrolyte are promising electrochemical energy conversion devices since they can operate without platinum group metals. In the past decade, AEMAFC performance has improved substantially due to improvements in electrode binders and AEM ionic conductivity. However, the alkaline (in)stability of AEMs is a significant hurdle that precludes commercialization of this technology. To date, there have not been any satisfactory strategies to adequately assess an AEM’s suitability for an AFC. Here, we report a best practices approach to evaluate a leading AEM candidate (poly(2,6-dimethyl 1,4-phenylene) oxide (PPO) with quaternary ammonium groups) for AEMAFCs. In this work, PPO AEMs were immersed in alkaline solutions at elevated temperatures and were characterized via functional tests (ion-exchange capacity and mechanical properties) and via two-dimensional NMR techniques. The data generated from these tests provided mechanistic insights into the degradation of PPO AEMs in alkaline conditions.