The damage and fracture behaviour of ductile metals is not only stress state dependent but is also influenced by plastic anisotropy arising from different sheet-metal manufacturing processes. This contribution focuses on analysing the damage and fracture behaviour of anisotropic ductile metals. The H-specimens are cut along different material orientations and subjected to loading paths generating different levels of stress triaxiality, facilitating the study of the effect of plastic anisotropy on damage evolution. Digital image correlation (DIC) is utilized to determine the strain fields on the surface of the specimen. Furthermore, the fractured surfaces of the specimen are examined with the help of scanning electron microscopy to better understand the damage evolution and fracture. From a numerical perspective, an anisotropic continuum damage model including the effects of plastic anisotropy is used to model the damage and fracture behaviour. The anisotropic Hoffman yield criterion is used to account for the strength-differential (SD) effect. Using this yield criterion, the stress state in the anisotropic ductile metal is characterized by generalized anisotropic stress invariants, together with the generalized stress triaxiality and the generalized Lode parameter. Moreover, microscale numerical analyses are performed to transfer microstructural information to the macroscale, capturing micro-defects, matrix behaviour, and their progressive evolution. The experimental results are compared with corresponding numerical simulations, highlighting the effectiveness of the experimental–numerical methodology in understanding the role of plastic anisotropy in ductile damage and fracture. On this basis, a fracture criterion expressed in terms of the damage strain tensor is proposed for anisotropic ductile metals. The developed experimental and numerical framework provides a systematic assessment of damage and fracture behavior of ductile metals.