The effects of post-welding heat treatment (PWHT) at temperatures ranging from 640°C to 750°C for 1 h on the mechanical and metallographical properties of a dissimilar-metal electron beam weld (EBW) joint of reduced activation ferritic/martensitic steel, F82H, and SUS316L austenitic stainless steel were investigated. The EBW joint is demarcated into five regions: the base metal of F82H (F82H-BM), the heat-affected zone of F82H (F82H-HAZ), the interlayer at the edge of F82H-HAZ (IL), the weld metal (WM), and the base metal of SUS316L (SUS316L-BM). No hardening resulting from welding and no significant change in the hardness resulting from PWHT above 640°C were observed in the F82H-BM, SUS316L-BM and WM. However, a significantly higher hardness was observed in the as-welded F82H-HAZ and IL than in other regions, and a significant reduction in hardness occurred in F82H-HAZ and IL, as a result of PWHT above 640°C. Irradiation hardening after PWHT at 720°C was investigated using proton-irradiation at 300°C up to 0.1 and 1 dpa. The irradiation hardening of the WM, IL and SUS316L-BM, which was less than that of the as-received SUS316L, was much larger than that of F82H-HAZ and F82H-BM.