This study aims to investigate the temporal and spatial attributes of the exit of Taiwanese enterprises from mainland China between 2001 and 2021, by applying enterprise database data. Furthermore, the influence of strategic coupling on Taiwanese enterprises’ exit from mainland China was also investigated. The following are the key findings: The spatial distribution pattern of the exit rate of Taiwanese enterprises in mainland China varied at different phases. In contrast, the inland regions of the country’s central and western zones, which are characterized by comparatively less developed economies, maintained consistently high exit rates, whereas the eastern coastal region retained a low exit rate. Particularly, the relationship between Taiwanese enterprises and the invested areas changed from Captive coupling to Cooperative coupling and subsequently to Absorptive Coupling. Similarly, the coupling modes significantly influenced the exit of Taiwanese enterprises from mainland China. Moreover, the COVID-19 pandemic has contributed to the backward connection of Taiwanese corporations, which have become more reliant on the mainland China market and local suppliers than earlier. Taiwan-favoring policies and the regional innovation environment have consequently emerged as the primary locational advantages for retaining Taiwanese enterprises in the aftermath of the global financial crisis. Therefore, the aforementioned factors may help to reduce the Taiwanese enterprises’ exit from mainland China and possess valuable policy implications for Taiwan investment zones in mainland China.