High strength pipeline steels have been increasingly applied for cost reduction of fuel transportation due to their excellent strength and toughness. Mechanical properties of the steels are influenced by microstructure and anisotropic characteristics, which were formed during the production. Neglecting these factors by designing pipeline system can lead to earlier susceptible pipe failure. In this work, anisotropies of the pipeline steel grade X65 were investigated by experiments and finite element (FE) based multi-scale modeling. Different microstructures at the center and skin of the pipe were considered. Tensile tests of specimens extracted from both regions under varying orientations were performed. The microstructure of pipe skin consisted of ferrite and lower bainite, whereas the central microstructure contained ferrite, cementite and M/A phase. FE simulations of 3D representative volume element (RVE) models were conducted to investigate effects of the existing phases. The anisotropic flow stress curves of the pipe predicted by the RVE approach fairly agreed with the experimental results. Afterwards, multi-scale FE simulations of pipeline subsidence were carried out. Two pipe conditions, namely, the skin and center area defined with the same and different properties were studied. Local stress and strain distributions of deformed pipe in different regions were compared and analyzed.