The “Belt and Road” has developed from a Chinese initiative to an international consensus, and Silk Road cities are becoming a strategic step for its high-quality development. From the perspective of industrialization, the “Belt and Road” can be regarded as a “spillover” effect of the industrialization process in China. With the spatial shift of Chinese industries along the “Belt and Road” and their clustering in Silk Road cities, the development and change of industrial land in Silk Road cities has become a new area of concern for governments and scholars. In this paper, the driving mechanism of industrial land change in 129 cities along the Silk Road in China is empirically studied by the Geo Detector method. The findings include: first, the development and changes of industrial land in Silk Road cities are significantly spatially heterogeneous, and the “Belt and Road” reshape the town system and economic geography along the route by virtue of the differentiated configuration and changes of industrial land, changing the social, political, landscape and spatial relations in cities on the line. Second, the driving forces of industrial land change in Silk Road cities under the influence of the “Belt and Road Initiative” are increasingly diversified and differentiated, with significant two-factor enhancement and non-linear enhancement interaction between two driving factors, and growing complexity of the driving mechanisms, requiring policymakers to design policies based on key factors, comprehensive factors, and their interaction. Third, the environmental effect of the industrial land change is highly complex. The industrial land quantity has a direct impact on the ecological state parameter and plays a decisive role in the quality of the ecological environment and its changes in Silk Road cities. However, changes in the industrial land affect the ecological state change indirectly, mainly interacting with it through the coupling of pollutant and carbon dioxide emissions, energy use, ecological planning, and landscape design and policy interventions. Finally, this study provides a new framework and method for Silk Road scholars to analyze the spatial and temporal evolution characteristics of land use and coverage in cities along the “Belt and Road” and their influence mechanisms and provides a basis for the government to make decisions on industrial land supply and layout planning and spatial governance policy design, which is of great theoretical significance and practical value