A series of clay shale specimens in equilibrium with various humidity conditions were used to establish the water retention characteristics, the influence of suction on ultrasonic p-wave velocity and rock mechanical properties such as Young’s modulus, Poisson’s ratio, onset of dilatancy, unconfined compressive strength and Brazilian tensile strength. Opalinus Clay, a clay shale considered as host rock for the disposal of nuclear waste in Switzerland was utilized. The results showed that the p-wave velocity normal to bedding (vp,n) dropped sharply upon desaturation until suction approached the air-entry value. The sharp decrease was associated with desiccation cracks solely oriented parallel to bedding. For suction in excess of the air-entry value, vp,n was constant, indicating no further desiccation damage. The suction at the shrinkage limit and at the air-entry point is similar in magnitude. The p-wave velocity parallel to bedding (vp,p) remained constant in the entire range of suction investigated in this study. The constant vp,p with increasing suction might be associated with the disproportional decrease in the Poisson’s ratio and Young’s modulus and its opposing effect on p-wave velocity. An almost linear increase in unconfined compressive strength, Brazilian tensile strength, stress at the onset of dilatancy and Young’s modulus with increasing suction was observed up to a suction of 56.6 MPa. For suction larger than 56.6 MPa, relatively constant strength and stiffness was observed. The increase is associated with the net contribution of suction to strength/stiffness, which decreases nonlinearly with decreasing volumetric water content. The rate of increase in tensile strength and unconfined compressive strength with increasing suction is different depending on the rock anisotropy. Compared to the strength values (Brazilian tensile and uniaxial compressive strength) obtained from specimens loaded parallel to bedding, the tensile strength parallel to bedding and the unconfined compressive strength obtained from specimens loaded normal to bedding are considerably more affected by increasing suction or decreasing water content. The reasons for the different rates in strength increase are considered to be related to local variations in suction (i.e., local suction) as a consequence of zones of contrasting pore-size distribution. These variations may influence the effect of suction on strength, especially when the load is applied parallel to bedding and crack growth occurs predominately along bedding layers with comparably low suction.