High-temperature polymer electrolyte membrane fuel cells (HT-PEMFCs) are gaining more and more attention due to their higher efficiency than low-temperature ones. Polybenzimidazole (PBI) membranes are the most popular membranes used in HT-PEMFCs. However, their chemical stability and chemical degradation mechanisms, which directly affect the lifetime of fuel cells, have been hardly reported. We applied the density functional theory and used ABPBI as an example membrane to investigate the chemical degradation mechanisms of PBI membranes. The possible degradation mechanisms that occurred on eight sites have been proposed, where sites 2 and 3 located on the phenyl ring are determined as two weak sites toward OH radical and oxygen molecule attack. When the terminal is the H atom at site 7, it is also weak under OH radical attack. Regarding these, the substituent effect on the chemical stability of polymers has been studied. By introducing four -C2F5 or -CN groups, the barrier heights of the corresponding degradation reactions are increased; thus, the chemical stabilities of related membranes are improved. The selection of terminal atoms was also explored for alleviating the chemical degradation of the membrane. The investigated proton transfer properties of nine model compounds revealed that introducing four -C2F5 or -CN groups improves the proton dissociation properties occurring at the cathode. The increase of phosphoric acid concentration is helpful for the proton transfer at both the membrane and the cathode. This work may hopefully help the design and synthesis of HT-PEMFCs with good stability and high efficiency.