Quantitative analysis of the spatiotemporal changes in China's industrial wastewater and the hidden driving factors can provide important information for the overall process management of industrial wastewater. Taking China's 31 provincial-level administrative regions as research objects, this paper employed spatial econometric (OLS) model and geographically weighted regression (GWR) model to evaluate the spatial spillover effects and identify the drive forces of wastewater discharge between provinces during 2004–2015 period. The results show that industrial wastewater discharge at the national level showed a trend of first increasing to 24.7 billion tons in 2007 and then decreasing to 19.9 billion tons in 2015. There was a significant positive spatial autocorrelation of industrial wastewater discharge among China's provinces and the emission hotspots were mainly concentrated in central-western China. Moreover, the nationalization level of industry, industrial structure and environmental protection measures were found to be major driving forces of the spatial changes of industrial wastewater discharge. Our findings indicated that strengthening industrial nationalization as well as encouraging cooperation between neighboring provinces may help to reduce the industrial wastewater discharge, which can pave the way for other developing countries that face similar water pollution problems.