The present study aims for dissimilar laser welding of maraging steel 250 and AISI 316 stainless steel thin sheets and investigates the mechanical properties and microstructure of the welded bead. The process parameters such as laser power, welding speed, and focal length were varied between 250–350 W, 100–300 mm/min, and 159–179 mm, respectively according to the Box-Behnken design (BBD) based on response surface methodology (RSM). Tensile tests were performed and results showed that high UTS and elongation (%) can be achieved in a high-power and low-speed configuration. The hardness test showed non-uniformity in the micro-hardness of most of the welded joint samples. Laser power and welding speed were found to have a greater effect on tensile strength while laser power, welding speed, and focal length showed a greater influence on percentage elongation. The optimization of the percentage elongation (EL) was found to be more desirable. The weld bead microstructure confirms the presence of epitaxial growth from the partially melted grains along both fusion lines. The columnar-dendritic structure was formed at the edge of the weld metal while both cellular dendritic structure and coarse equiaxed structure were formed near the center of the weld metal. The presence of iron and chromium along the stainless steel fusion line was confirmed by the formation of more elongated dendritic structures and micro-structural changes from cellular to columnar dendrites.