Standing seam metal roof systems are widely used in large-scale buildings such as factories, stations, and stadiums, while they are prone to have local and overall damages under strong wind due to the characteristics of lightweight and flexibility. It is crucial to study the wind-induced response and failure mechanism of standing seam metal roof systems, so as to improve their wind-resistance performance. Full-scale tests and numerical simulation were conducted to investigate the wind-induced response of standing seam metal roof systems, which includes the process of deformation, local buckling, and final failure. The displacement, failure modes, and ultimate bearing capacity of roof panel at different stages were studied under increasing wind loads. Results show that the failure mode of standing seam metal roof systems was the clip separation from seam. Local buckling was observed before the failure, which resulted in the global deformation of the roof panel. The clip force near the local buckling increased rapidly after the occurrence of the local buckling and caused the clip separation. The proposed finite element method can not only simulate the whole process of standing seam metal roof systems subjected to wind pressure but also predict failure modes and ultimate bearing capacity precisely.