Industrial heritage, recognized as a significant aspect of historical and cultural heritage, has garnered considerable attention from scholars globally. To elucidate the spatial morphological characteristics and the underlying influencing factors of industrial heritage within karst regions, this study employs methods such as the interstice index, fractal dimension analysis, and spatial syntax. It conducts research on the spatial morphological characteristics of nine typical industrial heritages in Guizhou Province. The primary factors contributing to the variations in layout forms are the intricate karst topography and the functional requirements of production. The functional zoning of industrial heritage aligns with its layout, characterized by straightforward functional zones that have not developed into composite spaces. The overall connectivity of industrial heritage is relatively low, exhibiting weak integration, significant disparities in control values, low average depth values, and a deficiency in comprehensibility and diversity of options. This indicates that the internal connectivity of industrial heritage spaces is generally inadequate, with low accessibility, strong interrelations, average convenience, limited connectivity, and generally acceptable passage. The overall spatial, architectural, and roadway configurations of industrial heritage predominantly exhibit a uniform pattern. Importantly, industrial heritage reveals a highly variable overall spatial form, with an average fractal dimension of 1.57, complex architectural layouts (average fractal dimension of 1.50), and simplistic road network designs (average fractal dimension of 1.43), which collectively suggest high spatial complexity and irregular characteristics. This study can provide a reference for the analysis of spatial characteristics and influencing factors of other material cultural heritages, and it is of great significance for the systematic protection and revitalization of industrial heritage.