Abstract: Offshore wind turbines are one of the important strategic choices for low-carbon sustainable energy, and their seismic safety issues need to be solved urgently. The three-dimensional seismic response problem of an offshore monopile wind turbine is regarded as a wave scattering problem, and the fluctuation input of the sea site is realized by combining with the artificial boundary conditions. A set of efficient zoning analysis methods for seawater—saturated seabed—wind turbine coupling are developed based on the unified calculation framework of generalized saturated porous media, and the three-dimensional seismic response analysis of the offshore monopile wind turbine is realized by comprehensively considering the soil-structure and fluid-structure interaction effects. The effects of seawater depth, wave velocity of seabed and incidence angle of seismic waves on the seismic response of the offshore monopile wind turbine are analyzed. The results show that the variation of seawater depth and shear wave velocity of seabed change the free field, and the self-vibration characteristics of the site—wind turbine system in the sea area, thereby affecting the seismic response of the wind turbine structure. When the seawater increases to a certain depth, the seismic response of the wind turbine increases sharply when the self-resonance frequency of the system is close to the input frequency of the seismic waves. The shear wave velocity of seabed has a greater influence on the bending moment at the bottom of the tower than on the displacement. When the incidence angle increases, the horizontal displacement and acceleration of the top of the tower and the bending moment at the bottom of the tower decrease to varying degrees, and the vertical displacement and acceleration at the top of the tower increase to different degrees. The nonlinearities of the seabed and wind turbine are not considered, and their influence laws needs to be further studied.