Spider silk-inspired fibers have attracted great attentions for their potential to combine high strength and high toughness. However, their production remains predominantly confined to the laboratory stage, hindered by formation continuity and performance stability upon scale-up. Herein, large-scale continuous production of spider silk-inspired multifilaments with high strength and toughness was realized using custom-designed spinning system. Coagulation bath was modulated to control solvent exchange process during spinning, thereby facilitating interfacial integration and improved molecular orientation. In addition, post-stretching process was optimized to further promote molecular orientation and crystal formation. After systematic process optimization, the large-scale continuous production of spider silk-inspired multifilaments with a robust and stable tensile strength of 234.54 ± 7.37 MPa and a toughness of 184.68 ± 20.91 MJ/m³ was achieved. This custom-designed spinning system enabled continuous spinning for more than 8 h, yielding multifilaments exceeding 18 km in length. This work provides a feasible strategy for the large-scale continuous production of spider silk-inspired multifilaments, bridging the gap toward practical applications.