This study aims to analyze the life-cycle primary energy and climate impacts of structural frames, paying particular attention to the design and prefabrication of different structural materials. The study considers an existing single-story office building with a composite concrete–steel structure and compares it with two functionally equivalent structures, i.e., a conventional reinforced concrete structure and a conventional steel structure. The existing building is located in San Felice sul Panaro, Italy. This study integrates dynamic structural analysis and life-cycle assessment (LCA). The study finds that the use of different materials can reduce the life-cycle primary energy use and CO2-eq emissions by up to 12%. Furthermore, the benefits derived from the recovery and recycling of materials can reduce the primary energy use and CO2-eq emissions by up to 47% and 36%, respectively. The prefabrication of structural elements can also reduce the primary energy use and CO2-eq emissions in the construction stage. A sensitivity analysis considers changes in the electricity supply system and shows that the primary energy and CO2-eq emissions due to prefabrication decrease when assuming marginal electricity based on renewable energies. This analysis supports the development of sustainable structural design to meet the standards concerning the whole-life-cycle carbon emissions of buildings.