Depressurization exploitation of hydrate in methane hydrate-bearing sediments (MHBS) causes changes in sediment effective stress, deformation, and hydrate content, often resulting in decreased permeability which reduces gas production efficiency. To investigate the evolution of MHBS permeability subjected to these changing conditions, permeability tests on MHBS of different methane hydrate saturation level were performed during isotropic compression and drained triaxial shearing under a wide range of effective stress conditions. The results of isotropic compression tests indicate that with increasing effective stress, MHBS permeability first decreases rapidly and then tends to stabilize, and the influence of hydrate saturation on permeability gradually reduces. The permeability during the triaxial shear process is closely related to volumetric deformation, with shear-contraction specimen exhibiting continuous decrease in permeability and shear-dilation specimens experiencing an increase in permeability. Unique correlation between permeability with effective void ratio (affected by hydrate saturation) was observed at low confining pressure and early stage of shear. However, this relationship becomes nonunique under increased pressure and shear strain. Thus, a unified MHBS permeability model for a range of conditions is established based on the observed relationship between MHBS permeability and effective void ratio, considering the influence of confining stress, shear strain, and the breakage of sediment particles.