Abstract: To investigate the interaction of heterogeneous solutes in the common molten pool flow during laser welding of heat-resistant steel and nickel-based alloy, a multiphase flow coupled welding model was established considering the combined induction of molten pool flow patterns and thermal physical property differences of dissimilar materials on element macro-segregation. The flow mixing of Fe-rich and Ni-rich molten metals and the formation process of Fe-rich segregation in the molten pool under different welding speeds were studied, and the rationality of the model was verified through comparison with experiments. The results indicate that in the upper part of the molten pool, the Fe-rich molten metal flows to the rear of the molten pool under the action of recoil force and Marangoni force. A portion of it flows forward after encountering the Ni-rich molten metal, forming band-like segregation near the fusion line in the middle of the molten pool; another portion enters the molten pool with Marangoni convection and mixes in the form of a vortex in the upper part of the molten pool. When the welding speed is 2.0 m/min, due to the fast solidification speed, the mixture is not uniform, forming a large area of block-like and vortex-like segregation, and the mass fraction of Fe element at the most severe segregation location reaches 80.29%. When the welding speed decreases to 1.2 m/min, the heat input of the molten pool increases, the solidification slows down; the area of the Fe-rich segregation region decreases; the segregation degree weakens, and the mass fraction of Fe element at the most severe segregation location decreases to 63.85%.