Dissimilar-metals joints between vanadium alloy NIFS-HEAT-2 (NH2) and nickel alloy Hastelloy X (HX) were developed by electron beam welding (EBW). If without filler, the joint fractured several minutes after the welding due to hard and brittle intermetallics formed in the weld metal (WM). Pure Ni filler with 0.2–1.0 mm in thickness decreased the content of intermetallics and eliminate hardening in the WM. However, there is always a hardening interlayer estimated as Ni2V and σ intermetallics, existed with thickness of 50 µm between NH2 base metal (BM) and WM. The hardening cannot be eliminated by annealing at high solution temperature of 1373 K. Aging at 723–973 K for 100 h further increased the hardening not only in the hardening interlayer but also in the WM. Pure Cu filler was also investigated. For the joint with 0.5 mm thick Cu filler, there are still hardening interlayer and hardening areas in the WM due to Ni2V and σ intermetallics. However, by increasing the Cu filler to 1 mm thick, the hardening interlayer disappeared by preventing mixture of NH2 and HX to form intermetallics. In this case, Charpy impact property of the joint with 1 mm thick Cu is much improved with ductile-to-brittle transition temperature (DBTT) less than 77 K. Even after thermal aging at 973 K for 100 h, the impact property did not degrade.