To investigate the effect of membrane thickness on the coupled electroporation–electrodeformation response of the cell membrane, a coupled model incorporating a dynamic Young’s modulus was developed to simulate transmembrane voltage, spatiotemporal pore evolution, and cell deformation at different membrane thicknesses. As membrane thickness increased from 6 to 10 nm, both the transmembrane voltage and pore radius peaked earlier. At 50 ns, pore density at the cell poles increased by 19.78%–67.44%, total electroporated area by 257.48%–859.36%, and the reduction in Young’s modulus became more pronounced. Despite increased membrane softening, peak Maxwell stress decreased by 26.15%–63.28% and remained the dominant factor, reducing peak displacement at the cell poles by 12.35%–34.75%. These findings show that membrane thickness modulates the coupled response by jointly affecting electrically induced pore formation, membrane mechanical properties, and Maxwell stress. The model provides a theoretical basis for designing pulse parameters for cells with different membrane structural characteristics.