During the drilling process, the drill string subjects to various alternating loads. Therefore, mechanics community has always been deeply studying its damage mechanism. In this paper, we first used the Python scripting language to establish a grain-size distribution model at the meso-scale on Abaqus software platform based on the basic principle of mesomechanics analysis. Then, the fracture mechanics algorithm—extended finite element method (XFEM) was applied to calculate the meso-scale grain model which contains micro-cracks and analyze the crack dynamic simulation propagation and distributions characteristics of stress and strain in this process. At last, by using the mesomechanics homogenization method, we handled the stress and the strain at different time, and obtained the effect of micro-crack propagation on macro-properties of drill string material. For drill pipe in elastic deformation stage at macro-scale, plastic zone may also exist at meso-scale and elasticity modulus is constant when there is no micro-cracks propagation. The idea of this paper can provide a new method for deeply exploring damage mechanism of drill string.