The gas extraction environment in coal seam exhibits uniaxial strain condition with constant overlying strata stress and horizontal strain. Simulating this environment in laboratory often ignores true triaxial stress state, so the difference in horizontal stresses reduction and the accompanying permeability evolution remain ambiguous. Therefore, this study conducted the true triaxial stress and permeability response tests simulating gas extraction environment under shallow and deep in-situ stress conditions. To quantify gas adsorption effect, the adsorbed (CO 2 ) and non-adsorbed (He) gases were also used. The results indicated that the intermediate and minimum principal stresses, i.e., σ 2 and σ 3 , exhibited a linear decreasing trend during gas depletion, but showed more decreases in stress when the intermediate and minimum principal strains, i.e., ε 2 and ε 3 , recover under high gas pressure depletion. High true triaxial stress enhanced the compressibility of pores and fractures in coal, resulting in low horizontal deformation and stress reduction gradient during gas depletion. Similarly, the reduction gradient of σ 2 , m σ 2, was less than that of σ 3 . This suggested that the difference between horizontal stresses also increased during coalbed methane (CBM) extraction, which exacerbated the risk of coal body damage. For different gas depletion, the stress reduction gradient exhibited m He < 1 and m CO2 > 1, which was related to the relative affinity of different gas species for the adsorption medium. A significant matrix shrinkage effect resulted in a more pronounced stress reduction. For permeability, the permeability increased exponentially during CO 2 depletion, while the permeability of helium exhibited a decreasing followed by an increase with decreasing gas pressure. This is related to the competing mechanism and synergistic effect of the adsorptive gas desorption, effective stress effect, and slippage effect. We quantified the contribution and mechanism of the three to the permeability separately. The permeability anisotropy ratio ( A r ) decreased exponentially during gas depletion. • Simulating true triaxial stress and permeability response during gas production. • σ 2 reduction gradient is less than that of σ 3 . In deep stress is less than shallow. • Stress reduction gradient of He ( m He <1) is much lower than that of CO 2 ( m CO2 >1). • Permeability anisotropy ratio reveals an exponential decrease during gas depletion. • Impact of desorption, effective stress, and slippage effect on k is quantified.