The infill walls are usually considered as nonstructural elements and, thus, are not taken into account in analytical models. However, numerous researches have shown that they can significantly affect the seismic response of the structures. The aim of the present study is to examine the role of masonry infill on the damage response of steel frame without and with various types of openings systems subjected to nonlinear static analysis and nonlinear time history analysis. For the purposes of the above investigation, a comprehensive assessment is conducted using twelve typical types of steel frame without masonry, with full masonry and with different heights and widths of openings. The results revealed that the influence of the successive earthquake phenomenon on the structural damage is larger for the infill buildings compared to the bare structures. Furthermore, when buildings with masonry infill are analyzed for seismic sequences, it is of great importance to account for the orientation of the seismic motion. The nonlinear static response indicated that the opening area has an influence on the maximal strength, the ductility and the initial rigidity of these frames. But the shape of the opening will not influence the global behavior. Then, the nonlinear time history analysis indicates that the global displacement is greatly decreased and even the behavior of the curve is affected by the earthquake intensity when opening is considered.