In the context of science and technological innovation, the spatial distribution and evolutionary patterns of cultural and creative enterprises tend to diversify, and their migration characteristics and mechanisms also change. Although traditional regional factors are difficult to explain the migration characteristics and mechanisms of cultural and creative enterprises effectively, amenity theory provides a new perspective for interpreting these characteristics. However, there is still relatively little research on amenities in China, and most of it focuses on national and regional scales, emphasizing conceptual interpretation, indicator construction, and evaluation. Few scholars have focused on the correlation between amenities and the spatial agglomeration of cultural and creative industries, and there have been few quantitative studies on the interaction between amenities and the relocation of cultural and creative enterprises. This study is based on the micro subjects of enterprises using UCINET social network analysis and geographic detectors to explore the migration characteristics and impact mechanisms of cultural and creative enterprises in Guangzhou from an amenity perspective. Research has shown the following: (1) Unlike the early evolution pattern of cultural and creative enterprises mainly gathering in the central area, and also different from the one-way migration path of manufacturing enterprises mainly transferring from the central area to the periphery, cultural and creative enterprises present more complex migration network relationships. The specific manifestation is that the urban center is not only the main place for enterprises to move in, but also the main place for them to move out. Both the migration and relocation modes dominate the central area, showing balanced diffusion and hierarchical decay, and the amenity preferences and migration characteristics of different types of enterprises tend to be diversified. (2) The influence of amenity factors on the migration of enterprises at different stages and types is heterogeneous, with factors such as leisure, social places, and transportation facilities having significant impacts. In contrast, the influence of landscape amenity factors is relatively low. The applicability of amenity factors varies regionally, domestically, and internationally. (3) The impact of amenities on the decision-making process of enterprise migration is mainly achieved through two types of entities: the enterprise and practitioners. The impact mechanism can be summarized into three aspects: the flow of enterprises in the central area under policy guidance, the return of enterprises under demand for supporting facilities, and the outward migration of enterprises under the assistance of policies and facilities. Specifically, the migration of large and medium-sized enterprises within the central area is often driven by their own development considerations. For enterprises that relocate from peripheral urban areas to central areas, the demand for amenity facilities from employees has gradually become a concern. Small- and medium-sized enterprises that relocate from the central to peripheral urban areas have higher autonomy and local mobility among their employees, and are more sensitive to environmental and policy amenities. Finally, based on the migration characteristics and impact mechanisms of cultural and creative enterprises, this study proposes strategic recommendations for creating cultural and creative spaces, developing cultural and creative industries, and shaping these amenities. The main contribution of this study to the existing literature is the exploration of the spatiotemporal migration characteristics of cultural and creative enterprises in Guangzhou from the perspective of new urban economic theory and summarization and improvement of existing research on the construction of amenity index systems. This study systematically reveals the impact mechanism of cultural and creative enterprise migration. Enriching and improving theoretical research on the interaction between amenities and creative enterprises can provide decision-making support for the high-quality development of Guangzhou's cultural and creative industries, as well as a reference for the spatial allocation and management of cultural and creative industries in other regions of the country.