This study investigates the seismic behavior of open-ground story (OGS) reinforced concrete buildings with soil-structure interaction (SSI) using SAP2000. The study mainly focused on mid-rise (8-storey) and low-rise (4-storey) OGS buildings, incorporating different masonry infill materials such as brick, concrete blocks, and autoclaved aerated concrete (AAC) blocks. Selected ground motions from the Bhuj, El Centro, and Chi-Chi earthquakes were utilized to simulate varying seismic intensities and frequency content. Critical parameters such as top-story displacement and inter-story drift are analyzed to assess the structural safety and serviceability of RC buildings. The results demonstrate that both OGS coupled with SSI and masonry infill type significantly affect the displacement and drift, with mid-rise buildings showing more pronounced impacts. Furthermore, ground motion characteristics are critical in producing different response patterns. The study highlights the importance of considering SSI, infill materials, and ground motion characteristics in the design of OGS buildings to enhance earthquake resilience and reduce seismic damage.