This study determines the relationship between permeability and other petrophysical properties in synthetic mudstones as a function of vertical effective stress. Six brine-saturated clay slurries consisting of smectite and kaolinite were compacted in the laboratory under both controlled pore pressure and proper drained conditions. Porosity, permeability, bulk density, velocity (both Vp and Vs) and rock mechanical properties were measured constantly under increasing vertical effective stress up to 50 MPa. The results show that smectite-rich clays compact significantly less and have lower bulk density, velocity, permeability, bulk and shear modulus but higher Poisson's ratio compared to kaolinite-rich clays at the same effective stress. Kaolinite aggregates compacted to about 26% porosity at 10 MPa effective stress corresponding to about 1 km burial depth in a normally compacted basin, whereas a pure smectite aggregate has a porosity of about 46% at the same stress. The permeability of kaolinite aggregates varies between 0.1 mD and 0.001 mD, while that of smectite aggregates varies from 0.004 mD to 0.00006 mD (60 nD) at stresses between 1 MPa and 50 MPa. Permeabilities in clays show a logarithmic decrease with increasing effective stress, bulk density, velocity or decreasing porosity. At the same porosity or bulk density, permeabilities differ up to five orders of magnitude within the smectite–kaolinite mixtures. Applications of the Kozeny–Carman equation for calculating permeability based on porosity in mudstones will therefore produce highly erroneous results. The relationships between Vp, Vs, bulk and shear modulus to permeability also vary by up to four orders of magnitude depending on the clay compositions. Velocities or rock mechanical properties will therefore not be suitable to estimate permeability in mudstones unless the mineralogy and textural relationships are known. These experimental results demonstrate that smectite content may be critical for building up pore pressure in mudstones compared to kaolinite. The results help to constrain compaction and fluid flow in mudstones in shallower parts of the basins (<80–100°C) where mechanical compaction is the dominant process. These results may also have implications for waste disposal and engineering practice, including structural design and slope stability analysis.