Abstract: The laser welding tests on 3 mm-thick and 6 mm-thick of Inconel 825 nickel-based alloy/AISI 321 stainless steel plates joints were studied. The influence of welding parameters on the weld formation was investigated, and the microstructure and mechanical properties of the welded joints were analyzed. The results indicate that for the 3 mm-thick test plate, the welding speed should be appropriately reduced, the gas escape time should be prolonged to eliminate the metallurgical type porosity. A well-formed weld can be obtained on vertical welding position with the laser power of 3 kW, the welding speed of 1.7 m/min and the defocus of 0 mm. For the 6 mm-thick test plate, the laser power and defocus should be increased, and the stability of the key-hole should be enhanced to eliminate the process type porosity. A well-formed weld can be obtained with the welding gun tilted back by 6°, the laser power of 8 kW, the welding speed of 1 m/min, and the defocus of +3 mm. The microstructure in the weld zone is dendritic Fe-Ni-Cr-based solid solution and a small amount of dispersed Ti-rich precipitates, and the grains in the heat affected zone hardly grow. The dissimilar welded joints of the two materials possesses good tensile strength and plasticity, and the fracture mode is ductile fracture. The rapid cooling of laser welding leads to insufficient carbide precipitation, which is the main cause for the lower hardness of the weld zone compared to the base material.