A combination of permeability and ultrasonic velocity measurements allied with image analysis is used to distinguish the primary microstructural controls on effective-pressure-dependent permeability. Permeabilities of cylindrical samples of Whitby mudstone were measured using the oscillating pore-pressure method at confining pressures ranging between 30 and 95 MPa, and at pore pressures ranging between 1 and 80 MPa. The permeability–effective pressure relationship is empirically described using a modified effective pressure law in terms of confining pressure, pore pressure and a Klinkenberg effect. Measured permeability ranges between 3×10−21 and 2×10−19 m2 (3 and 200 nd), and decreases by approximately one order of magnitude across the applied effective pressure range. Permeability is shown to be less sensitive to changes in pore pressure than changes in confining pressure, yielding permeability effective pressure coefficients (χ) between 0.42 and 0.97. Based on a pore-conductivity model, which considers the measured changes in acoustic wave velocity and pore volume with pressure, the observed loss of permeability with increasing effective pressure is attributed dominantly to the progressive closure of bedding-parallel, crack-like pores associated with grain boundaries. Despite only constituting a fraction of the total porosity, these pores form an interconnected network that significantly enhances permeability at low effective pressures.