The alkaline stability of N‐heterocyclic ammonium (NHA) groups is a critical topic in anion‐exchange membranes (AEMs) and AEM fuel cells (AEMFCs). Here, we report a systematic study on the alkaline stability of 24 representative NHA groups at different hydration numbers (λ) at 80 °C. The results elucidate that γ‐substituted NHAs containing electron‐donating groups display superior alkaline stability, while electron‐withdrawing substituents are detrimental to durable NHAs. Density‐functional‐theory calculations and experimental results suggest that nucleophilic substitution is the dominant degradation pathway in NHAs, while Hofmann elimination is the primary degradation pathway for NHA‐based AEMs. Different degradation pathways determine the alkaline stability of NHAs or NHA‐based AEMs. AEMFC durability (from 1 A cm−2 to 3 A cm−2) suggests that NHA‐based AEMs are mainly subjected to Hofmann elimination under 1 A cm−2 current density for 1000 h, providing insights into the relationship between current density, λ value, and durability of NHA‐based AEMs. This work systematically explores the alkaline stability and degradation mechanism of 24 representative N‐heterocyclic ammonium groups and poly(aryl piperidinium)‐based polyelectrolytes for anion‐exchange‐membrane fuel cells (AEMFCs), providing a clear guideline for design of highly stable anion‐exchange membranes and ionomers. The structure–durability relationship between ammonium groups, anion‐exchange polyelectrolytes, and AEMFCs was revealed.