The overexploitation of groundwater in China has raised concern, as it has caused a series of environmental and ecological problems. However, far too little attention has been paid to the relationship between groundwater use and the spatial distribution of water users, especially that of manufacturing factories. In this study, a factory scatter index (FSI) was constructed to represent the spatial dispersion degree of manufacturing factories in China. It was found that counties and border areas between neighboring provinces registered the highest FSI increases. Further non-spatial and spatial regression models using 205 provincial-level secondary river basins in China from 2016 showed that the scattered distribution of manufacturing plants played a key role in groundwater withdrawal in China, especially in areas with a fragile ecological environment. The scattered distribution of manufacturing plants raises the cost of tap water transmission, makes monitoring and supervision more difficult, and increases the possibility of surface water pollution, thereby intensifying groundwater withdrawal. A reasonable spatial adjustment of manufacturing industry through planning and management can reduce groundwater withdrawal and realize the protection of groundwater. Our study may provide a basis for water-demand management through spatial adjustment in areas with high water scarcity and a fragile ecological environment.