Past earthquakes have shown that masonry walls are vulnerable to fail near the openings. Openings such as doors and windows are an essential part of the structure. The presence of an opening reduces the strength and stiffness of the masonry structures. It also affects the load-resistant mechanism of the masonry walls. The walls are subjected to simultaneous in-plane and out-of-plane forces during seismic events. Therefore, the analysis of the masonry walls either in in-plane or out-of-plane direction may not give a proper picture of the global behavior of the masonry structures. The masonry walls deform primarily in the in-plane direction if the walls are properly tied with each other, and the structure is constructed by following codal provisions. Under this situation, it is necessary to investigate the effect of in-plane damage on the out-of-plane strength of the masonry walls. Few researchers have studied the behavior of solid unreinforced masonry walls under combined loading. However, limited work can be found for masonry walls with openings. Therefore, the present study focuses on the effect of different types of opening layouts on the combined in-plane and out-of-plane behavior of masonry walls incorporating varying pre-compression. Further, in masonry buildings, walls are interconnected, making the masonry walls of various shapes. In this study, masonry walls of rectangular and I shapes have been considered to examine the effect of cross-walls under combined loading. Interaction curves have been developed for the walls subjected to the in-plane loading followed by an out-of-plane pressure. Based on the results, the maximum opening percentage in the masonry walls has been suggested, which is desirable in the case of masonry buildings constructed in high seismic zones.