Understanding the embrittlement of reactor pressure vessel (RPV) steels at high fluence region is very important for the long term operation of nuclear power plants. In this study, extensive microstructural analyses were performed on the RPV steels irradiated to very high fluences beyond 10²⁰n/cm², E>1 MeVat high fluxes under the Pressurized Thermal Shock and Nuclear Power Plant Integrity Management projects in Japan. Three dimensional atom probe analyses were performed to characterize the solute atom cluster formation in these materials. The effects of fluence, flux, and chemical compositions on the characteristics of clusters were analyzed. The formation of dislocation loops was identified in the transmission electron microscopy analyses of high and low Cu steels, and the changes in loop size and number density with fluence were studied. P segregation on grain boundaries was also studied by surface analyses as well as grain boundary chemical analyses. We found that nonhardening embrittlement due to grain boundary fracture is not a major contributor to the embrittlement in these materials and irradiation conditions. The correlation of the microstructural changes and the Charpy transition temperature shifts was studied. The volume fraction of solute atom clusters has an excellent correlation with the transition temperature shifts. The Orowan model calculations of the contributions of dislocation loops to the transition temperature shifts show that in low Cu materials, dislocation loops may be a major contributor, but in Cu containing materials its contribution is weak. Root-sum-square of the contributions of solute atom clusters and dislocation loops seems to be a reasonable model to describe the total ΔRT_NDT.