The weld microstructure is significantly related with the performance of welded joints during the laser welding. Compared to the two-dimensional microstructural morphology, the three-dimensional weld grain morphology has more important information with the quality of welded joints. Therefore, a method is proposed for reconstructing the three-dimensional morphology of weld grains in laser welding of 6061 aluminum alloy based on octree regularization, which is extremely helpful for the observation and analysis of microstructure during the laser welding. The point cloud density is effectively reduced by utilizing octree regularization during the reconstruction process and the balance between reconstruction efficiency and reconstruction accuracy is improved. The reconstructed three-dimensional morphology of the weld grains is compared with the results obtained from numerical calculation. It is found that the reconstruction results effectively characterize the size of weld grains and the spatial distribution and achieve the enhanced reconstruction efficiency under the high reconstruction accuracy condition. Notably, the reconstructed result reveals the spatial distribution pattern of weld grains, which is difficult to be detected from two-dimensional metallographic observations of the weld microstructure. Therefore, the proposed method is of great importance for analyzing the weld microstructure quantitatively and evaluating the performance of welded joints during the laser welding.