The girth weld is the weak link of high-pressure pipeline, which is easy to crack under the combined action of internal and external loads, defect and stress concentration. At present, the safety hazards of high-strength pipeline girth welds are prominent, and it is of great significance to study the failure law of girth welds to ensure the safe operation of pipelines. In this paper, the failure analysis of 6 welded joints with crack defects excavated on site in a gas transmission company was carried out. Through metallographic analysis, scanning electron microscope (SEM) observation and electron backscatter diffraction (EBSD) analysis, the relationship between root welding, weld microstructure and crack generation was analyzed in detail. The influence of grain boundary distribution behavior of weld microstructure on crack propagation path was studied, and the mechanism of welding inclusions on crack propagation and aggregation nucleation was revealed. The results show that the cracks in root welding, hot welding, filling welding and heat affected zone are all transgranular propagation types, and the deflection of crack propagation path may be related to the complex stress state at the welded joint. Local strain concentration often exists in the near crack surface, secondary crack and crack deflection position on the crack propagation path, which indicates that the formation and propagation of root cracks are likely to be related to the deterioration of weld metal properties caused by local strain concentration at the root. The research conclusions have certain reference value for the intrinsic safety design, construction, and integrity operation and maintenance of pipeline girth welds.