Increasing interest has recently been devoted to interlocking blocks/interfaces capable to enhance the sliding resistance of masonry joints to external forces. In this framework, this paper deals with the assessment of the torsion-shear capacity of the contact interface between the lock and the main body of an interlocking block, assumed to have a cohesive behaviour. The interlocking block is a rigid unit which, on its faces, have square cuboidal locks keeping the adjacent/overlapped blocks together and preventing blocks from sliding. Two numerical approaches and a novel ad hoc experimental investigation are proposed to simulate the torsion-shear behaviour by applying eccentrical shear forces to the lock. First, concave, convex and corrected concave formulations provided by the literature for assemblages of rigid blocks with conventional planar joints are extended to model the interlocking block behaviour. Then, according to a second approach based on the discrete element method, the concave-shaped interlocking block is modelled by convex polyhedrons representing the lock and the main body of the block, considered as individual rigid units stacked over each other with a cohesive contact in between. A novel experimental investigation on the limiting pure shear and torsion-shear combinations at the lock interface made of cohesive material is also presented. Two different mortars were chosen to make the specimens, which were casted using 3D printed moulds, and different test configurations were set up to simulate shear and torsion-shear failures. The analytical and numerical results are compared with each other and against the experimental ones, with interesting remarks on the application of the different approaches.