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While openings are an essential requirement in buildings as a source of access, fresh air and sunlight, these openings cause a reduction in the lateral stiffness and torsional resistance of masonry wall units. A detailed numerical investigation was carried out to explore the impact of the opening percentage on the in-plane stiffness and lateral strength of unconfined and confined masonry wall panels prepared using calcium silicate bricks, for sustainable masonry structures. A commercially available FEM package (ANSYS) was used to carry out comparative analysis of ten wall panels, five of each type (confined and unconfined masonry walls) with concentrically located openings of varying sizes (0% to 16.5%). A simplified micro-modeling technique following the Newton Raphson Algorithm was adopted. Results revealed that the confined masonry approach unveiled a more reliable anti-seismic response along with improved in-plane strength in the case of confined masonry walls. The failure type shifted from pure flexural to more of a blend of shear and flexure after the opening percentage increased to 10.09% in unconfined masonry walls, which was not the case where confinement was provided. Based on the outcomes, it is strongly recommended to adopt confined masonry in highly seismic-prone areas to avoid catastrophic damage caused by earthquakes.