It is of great significance to reveal the microevolution mechanism of welded structures during thermo-mechanical coupling to improve the welding quality. In this paper, a random microcrystalline structure model for welds is established by the Voronoi tessellation method. According to the nanoindentation results, heterogeneous grains are produced. A welding workpiece model with statistical significance is established. On this basis, the Python script and the birth and death element method are used to realize the transient growth of a weld, and a thermo-mechanical coupling model for the SUS301L-HT stainless steel metal inert gas welding process is established. The temperature field and thermal stress field are calculated. The calculation shows that the thermal stresses along the growth direction of the weld area are in the form of a “trapezoid,” and the stresses at both ends are small. The stress in the vertical direction of the weld has a single peak, and the peak appears in the center of the weld. The stress distribution of the model that considers heterogeneous grains is obviously inhomogeneous compared with that of the traditional model. The thermal stress distribution in the weldment is obviously inhomogeneous due to the heterogeneous grains, the stresses at the boundaries of the adjacent grains in the weldment change abruptly. It is found that the greater the difference in the mechanical properties between grains is, the more obvious the change.