The Hastelloy X superalloy is a widely used solid-solution Ni-based sheet alloy for gas turbines, aero-engine combustion chambers, and other hot-end components. To investigate the effect of microstructure, especially grain size, on its weldability, Hastelloy X alloy bars are homogenized, cold-rolled to thin sheets, and recrystallized under different conditions to obtain equiaxed grain microstructures with average grain sizes of ~5 μm, ~12 μm, and ~90 μm. The laser welding process is used for joining the alloy sheets, and then the alloy’s weldability is investigated through microstructural and mechanical property characterizations. The microstructures in weld consist of coarse columnar grains with dendrite, and grain sizes of these columnar grains are almost the same when grain size of Hastelloy X base metal increases from ~5 μm to ~90 μm. Moreover, although all welds exhibit lower yield strengths (YS), ultimate tensile strengths (UTS), and elongations to fracture (EF) than the base metal, the degrees of reduction in them become slight when the grain size of base metal increases from ~5 μm to ~90 μm.