The geological sequestration of CO2, underground coal mining, and coalbed methane production in deep coal reservoirs is executed under high levels of 3-D geo-stress, and it is accompanied by significant variations in both vertical and horizontal stresses. In addition, coal is a highly fractured porous medium characterized by complex natural fracture systems. This exterior and interior anisotropy complicates the replication of in situ conditions in the laboratory. In this study, we divided pre-existing fracture systems of cubic coal into three flow planes: a bedding plane, face cleat plane, and butt cleat plane. Gas flowed through cubic coal samples along each flow plane under differently designed true triaxial stress paths. We then further analyzed anisotropic mechanical and flow property responses of cubic coal after failure by model fitting, CT scan reconstruction, and fractal representation. The experimental results indicate that pre-existing flow planes play significant roles in the strength levels, failure modes, and permeability levels. Low strength levels, typical shear failure patterns, and low initial permeability levels were observed in the butt cleat plane direction. Anisotropic strength data can be effectively fit by applying a linear relationship between octahedral shear stress and mean effective normal stress. After coal failure, the peak permeability observed in the face and butt cleat plane directions also presents a strong linear relationship with the fractal dimension. An anisotropic conceptual failure process model was established for the description of internal fracture development during stress loading. Horizontal stress unloading decreased the strength and formed a more complex fracture system in cubic coal regardless of the different flow planes involved, producing the increments of associated peak permeability.