This study examines the general load-displacement behavior of reinforced concrete frames with opening masonry infill walls in different sizes and locations under lateral earthquake loading. In addition, a strengthening detail was developed with anchored CFRP strips to reduce the negative effects of openings in masonry infill walls on the performance of reinforced concrete frames with infill walls. Experimentally, it was investigated to what extent the proposed strengthening method could improve reinforced concrete frames and masonry infill walls with openings. The variables examined in this study were determined as the size of the openings left in the masonry infill walls and their location in the frame. As a result of the tests of the first series of test specimens in the experimental program, the negative effects of the openings left in the masonry infill walls on the performance of the infilled wall frame systems under the effect of earthquake loading were determined. Within the scope of the study, the effectiveness of the strengthening method with the infilled test specimens was determined in the second series. Within the horizon of the study, the strengthening method developed with anchored Carbon-Fiber-Reinforced-Polymers (CFRP) strips increased the ultimate load capacity, initial stiffness, displacement ductility ratio, and energy dissipation capacity values of the masonry infilled frame systems with opening by an average of 72%, 11%, 13%, and 10%, respectively.