New regulatory requirements in Japan have strengthened the mitigation of damage caused by natural hazards, such as earthquakes, and the operational guide for safety improvement evaluation recommends the use of a probabilistic risk assessment (PRA) as the evaluation method in Japan. In the PRA of an earthquake, also known as the seismic PRA, one of the most important issues is the realistic assessment of the structural seismic response and the conditional damage probability (fragility) assessment using a realistic response assessment of nuclear buildings and equipment. Accordingly, we conducted this study both on the analysis methods used for realistic seismic response and assessment methods of seismic fragility to ensure the seismic safety of nuclear buildings and equipment. In this study, we use a three-dimensional (3D) structural model of a reactor building to conduct a nonlinear seismic response analysis for input ground motions beyond a design basis. In addition, we identify the failure mode of the structural components of the reactor building associated with the equipment and assess the seismic fragility based on the 3D behavior of the reactor building. The local response and detailed damage progress of the reactor building obtained through seismic response analysis are reported, along with the results of the seismic fragility assessment.