This work is a two-part article series on chemo-mechanical membrane degradation in fuel cells, wherein Part 1 investigated edge failure and the present work in Part 2 investigates failure within the active area of an edge-protected cell. X-ray computed tomography based 4D visualization with three spatial dimensions plus one time dimension is applied to capture the progress of membrane degradation under chemo-mechanical accelerated stress testing. Buckling driven membrane cracks are found to be the predominant failure mechanism, occurring exclusively under the uncompressed flow field region. In situ electrochemical diagnostics show significant gas crossover and dramatic open-circuit cell voltage loss accompanying membrane crack formation. The observed root cause of membrane buckling is facilitated by pre-existing cracks and surface pores in the catalyst and microporous layers, which enable hygral expansion and locally amplified compressive-tensile stress cycles in the membrane. Moreover, permanent membrane creep into gas diffusion layer pores is identified exclusively under the compressed land region, which is driven by locally elevated compressive stress in the membrane. Chemical stress is inferred to be a contributing, accelerating factor in this degradation process as a uniform, global effect rather than a locally amplified cause of failure. • 4D in situ visualization is used to elucidate chemo-mechanical membrane degradation. • Membrane failure in the active area is captured after MEA edge protection. • Through-thickness membrane cracks under channels is the primary failure mode. • Membrane creep and catalyst layer deformation is observed under land regions. • Several root causes of failure are identified and discussed.