Large-scale personalization is becoming a reality. To ensure market competitiveness and economic benefits, enterprises require rapid response capability and flexible manufacturing operations. However, variant design and production line reconfiguration are complicated because it involves the commissioning, replacement, and adaptive integration of equipment and remodification of control systems. Herein, a digital twin-driven production line variant design is presented. As a new technology, the digital twin can realize the parallel control from the physical world to the digital world and accelerate the design process of the production line through a virtual–real linkage. Simultaneously, the actual production line can be simulated to verify the rationality of the design scheme and avoid cost wastage. Four key technologies are described in detail, and a production line variant design platform based on digital twin is built to support rapid production line variant design. Finally, experiments using a smartphone assembly line as an example are performed; the results demonstrate that the proposed method can realize production line variant design and increase production efficiency.