Flexible connection between the wall and the frame can improve the seismic performance of the structure, thus minimizing the pushing effect of the infill wall on the main frame. Masonry infill walls with flexible connection have lower out-of-plane stability than walls with rigid connection. However, local collapses are more likely to occur. A comparative study was conducted on the load-carrying capacity, initial stiffness, deformation and ductility of different wall structures based on a monotonous static load test, and the out-of-plane mechanical properties exhibited by flexible masonry infill walls were investigated. A simplified separated finite element model of masonry infill wall was built in accordance with the test results, and then the monotone out-of-plane static loading was performed. The structural configuration, the wall-frame connection method, and the spacing between structural columns were found to have significant effects on the out-of-plane mechanical behavior of the infill wall. The wall structural configuration was found to have the strongest effect, followed by the wall-frame connection method. Under the conditions of flexible connection, when the wall structure was in the “grid-beam” form, and the spacing between structuring columns was 2.5–3.0 m, the frame-infill wall was found with the best restraint effect, so the optimal out-of-plane comprehensive mechanical performance would be achieved.