Polymer electrolyte membrane fuel cells (PEMFCs) has been widely considered as the most promising power sources for electric vehicles due to their ultimate cleanness, high efficiency and fast refueling. Recently, the increased scalability of power and energy in fuel cells has made the PEMFC an ideal power plant for heavy-duty vehicles (HDVs), i.e., electric long-haul trucks and coaches, with different drive cycles and operating conditions, which requires more durable catalyst and membrane compared with light duty vehicles (LDVs). Unfortunately, the degradation mechanism of the catalyst and membrane in membrane electrode assembly (MEA) of PEMFCs during long-period operation under the HDV condition is still not clearly understood. In this work, MEAs were made of our highly active catalysts, 30wt% Pt/KB, as the cathode and a commercial Pt/C catalyst as the anode. The MEAs were tested at different relative humilities under the HDV conditions with catalyst loading of 0.2 mg_Pt/cm², back pressure of 250 kPa, under the standard protocol of accelerated stress test (AST) for 180k cycles, which is equivalent to 30,000 h. The results show that the MEA exhibit very high performance at beginning of life (BOL) with a current density of 1.6 A/cm² at the cell voltage of 0.7 V, high mass activity of 384 mA·mg_Pt and large electrochemical active surface area (ECSA) of 86 m²·g_Pt at 50%RH. Under the same testing condition, the MEA still maintained the current density of 1.4 A/cm², 1.2 A/cm² and 1.0 A/cm² and 0.9 A/cm² at the cell voltage of 0.7 V after the AST of 30k, 60k, 90k and 120k cycles. Moreover, the performance of the MEA significantly decreased to 0.5 A/cm² and 0.3 A/cm² at the voltage of 0.7 V after the AST of 150k and 180k cycles. In comparison, the mass activity of the MEA first significantly dropped to 183 mA·mg_Pt after the AST of 30k cycles and maintains uniform decreasing from 60k cycles to 180 cycles, the similar phenomenon was observed in the degradation of ECSA. The H₂ crossover and AC impendence spectra of the MEA was measured at different cell voltage during the AST process, in order to study the kinetic and mass transport loss during the degradation. Furthermore, the Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) was performed on the produced water of the MEA to monitor the degradation of Pt nanoparticles, carbon support, ionomer, and membrane. Besides, the Pt migrations, the pore structure and volume change in the carbon support before and after the AST of 180k cycles were studied using HR-TEM and mercury intrusion porosimetry (MIP). During the whole AST testing cycles, the MEA exhibited higher performance at relatively low humidity level, which is associated with the insufficient hydrophilicity of the carbon support and is more favorable for the PEMFCs working in low-humidity condition. In summary, this work presents the degradation behavior and mechanism for highly efficient and durable PGM-catalyst MEA under HDV conditions.