Anisotropy is an important property that is widely present in crustal rocks. Efforts have been devoted to providing a constitutive model that can describe both inherent and stress-induced anisotropy in rock. Different from classic models, that are based on stress invariants or strain tensors, we propose here an anisotropic damage microplane model to capture the characteristics of rock properties in different orientations (i.e., their anisotropy). The basic idea is to couple continuum damage mechanics with the classic microplane model. The stress tensor in the model is dependent on the integration of microplane stresses in all orientations. The damage state of any element in the model is determined by the microplane that satisfies the maximum tensile stress criterion or Mohr–Coulomb criterion. An ellipsoidal function was used to characterize the failure strength, where the orientation of the failure plane changes with the preferred orientation of defects in the rock. The proposed model is validated against laboratory experiments performed on brittle material with orientated cracks and granite under true triaxial compression. The fracture pattern and the effect of the intermediate principal stress are numerically predicted by our anisotropic damage model and we discuss relationships between the damage evolution and the anisotropy of the rock under true triaxial compression. The proposed numerical model, based on microplane theory, offers a new approach to analyzing the effect of crack orientation on the deformation and fracture of brittle rock.