A hybrid experimental and numerical investigation has been conducted to comprehensively characterize the anisotropic plasticity and ductile fracture behavior of a high-strength pipeline steel. Tensile tests have been performed on various flat specimens along three different loading directions to collect the experimental mechanical data covering a wide range of stress states. For numercial modeling, the anisotropic plastic deformation is described by the evolving non-associated Hill48 (enHill48) plasticity model considering anisotropic/distortional hardening and evolution of r-value. Based on the enHill48 model, in this study, an anisotropic damage mechanics model with consideration of the evolution of anisotropy and stress states has been proposed and calibrated to predict the anisotropic damage and fracture of the investigated material. It is concluded that the anisotropic hardening is critical for an accurate prediction of the ductile fracture. The proposed model has achieved good predictive capability for anisotropic fracture behavior.