Due to the influence of masonry infill walls, the effects of the short column will be produced in the reinforced concrete (RC) frame column, and the RC column will be subject to serious earthquake damage. In the field of masonry infill wall RC frame structure collapse prevention in strong earthquakes, it is important to accurately simulate the seismic damage behaviors of the RC frame column while considering the influence of an infill wall with openings. Firstly, a segmentation equivalent nonlinear spring simplified model is proposed to consider the influence of the infill wall with openings, and the value of the restoring spring force in the simplified model is given. Then, based on the simplified model, the nonlinear seismic damage behavior of an RC frame column in an actual bottom frame structure is simulated, and the numerical simulation results are compared with the actual earthquake damage to verify the effectiveness of the simplified model. Finally, the seismic damage evolution mechanism of the frame column in the bottom frame structure is analyzed, and the influence laws of the infill wall with openings on the RC frame column are discussed. The research shows that the simplified analysis model can effectively simulate the influence of infill walls with openings on the seismic damage of the RC frame column. The opening infill wall leads to the short column effect, and the frame column can easily present brittle shear failure. Therefore, the seismic design of the frame column near window-height should be highly considered.