The growing demand for energy-efficient and environmentally sustainable building materials has led to an increasing interest in hybrid timber-concrete construction. These structures combine the advantages of the two materials, potentially reducing the carbon footprint, shortening construction timelines, and improving seismic and building physics performance. Herein the structural and environmental performance of ten-story timber-concrete hybrid and a pure concrete building, designed for the Guizhou Province, China, were compared. The structural analysis revealed a significant reduction in the self-weight and base shear of the hybrid structure. The life-cycle analysis demonstrated that the hybrid building outperformed the concrete building in six categories, including global warming potential, acidification potential, human health particulate, eutrophication potential, ozone depletion potential, and photochemical ozone formation potential. Notably, the hybrid building exhibited nearly 65% lower emissions in terms of global warming potential. Moreover, the inclusion of wood components offered the added benefit of carbon storage throughout their lifespan. These findings provide compelling support for the development and implementation of high-rise timber-based hybrid buildings in China. The advantages observed in both structural and environmental aspects encourage the adoption of this innovative construction approach, contributing to sustainable and eco-friendly building practices.