The fracture toughness of nanostructured materials depends on anisotropic physical properties of individual microstructural features, their texture and/or topology. In this work, intentionally sculptured grain boundaries of low cohesive energy were used to form “weak” and “tough” crack propagation directions within a nanocrystalline TiN film, allowing to correlate the directional arrangement of grains and anisotropy of fracture toughness. By using a selective micromechanical testing approach, two different cracking directions were probed in a scanning electron microscope by loading microcantilever beam specimens prepared parallel and perpendicular to the stacked direction of the alternately tilted columnar grains. The fracture toughness along the sculptured grain boundaries was ~30% higher due to effective multiple crack deflection at the kink planes, which was not observed along weak cleavage planes in the stacked direction. The results indicate the fundamental importance of microstructural design in the synthesis of tough nanostructured ceramics, whose anisotropic mechanical properties can be controlled effectively by incorporating dedicated microstructural features of well-defined topology, orientation and density.