We demonstrate a comprehensive earthquake response analysis method for improving the seismic input force estimation of buried pipelines by combining ground motion and soil amplification analyses. Using this method, the seismic input force of an actual pipeline was estimated and its seismic performance was checked for a largest assumed seismic fault scenario. Three-dimensional inhomogeneity of ground and surface topography is known to greatly affect the results of ground motion and soil amplification analyses. To consider these effects, a linear wave propagation analysis using a 10 × 109 degree-of-freedom three-dimensional finite element model was conducted for the ground motion analysis, and a nonlinear wave propagation analysis using an 80 × 106 degree-of-freedom three-dimensional finite element model was conducted for the soil amplification analysis. The application example showed that three-dimensional inhomogeneity of ground and surface topology caused complex seismic input forces to buried pipelines, and demonstrated the effectiveness of the comprehensive seismic analysis method proposed in this study.