Conductivity of fluids along fractures in all rocks is reduced by increasing normal stress. For sandstones and other hard rocks the onset of shear failure along planar cracks is thought to enhance fluid flow owing to a small amount of dilatancy, yet such effects are poorly quantified. Here we determine experimentally how independently increasing normal and shear stress affects fluid flow along fractures in shale. Gas flow along bedding-parallel planar interfaces was measured for flow parallel and normal to the shear direction. Increasing shear stress causes accelerating reduction of conductivity, even before the onset of macroscopic slip. Such reduction in fluid flow rate is non-recoverable, and the combined effects of normal and shear stress can reduce fracture conductivity by more than 3 orders of magnitude over the range of shale reservoir conditions. Bedding plane-parallel slip is common in shales; it can result in a large enhancement of permeability anisotropy, because flow across bedding planes becomes inhibited. This can impact upon the geometry of developing hydraulic fractures, encouraging complexity and favouring lateral relative to vertical growth. The results will facilitate modelling of fluid flow through fracture networks.