Characterizing irradiation damage in materials utilized in light water reactors is critical for both material development and application reliability. Here we use both nanoindentation and Laue microdiffraction to characterize both the mechanical response and microstructure evolution due to irradiation. Two different irradiation conditions were considered in 304 stainless steel: 1 dpa and 10 dpa. In addition, an annealed condition of the 10 dpa specimen for 1 h at 500 °C was evaluated. Nanoindentation revealed an increase in hardness due to irradiation and also revealed that hardness saturated in the 10 dpa case. Broadening using Laue microdiffraction peaks indicates a significant plastic deformation in the irradiated area that is in good agreement with both the SRIM calculations and the nanoindentation results.