Ion irradiation is often used to simulate the effects of neutron irradiation due to reduced activation of materials and vastly increased dose rates. However, the low penetration depth of ions requires the development of small-scale mechanical testing techniques, such as nanoindentation and microcompression, in order to measure mechanical properties of the irradiated material. In this study, several candidate structural alloys for Gen-IV reactors (800H, T91, nanocrystalline T91 and 14YWT) were irradiated with 70 MeV Fe9+ ions at 452 °C to an average damage of 20.68 dpa. Both the nanoindentation and microcompression techniques revealed significant irradiation hardening and an increase in yield stress after irradiation in austenitic 800H and ferritic-martensitic T91 alloys. Ion irradiation was observed to have minimal effect on the mechanical properties of nanocrystalline T91 and oxide dispersion strengthened 14YWT. These observations are further supported by line broadening analysis of X-ray diffraction measurements, which show a significantly smaller increase in dislocation density in the 14YWT and nanocrystalline T91 alloys after irradiation. In addition, good agreement was observed between cross-sectional nanoindentation and the damage profile from SRIM calculations.