Abstract: Decomposing the driving effect of spatio-temporal differences in production water use and domestic water use in the Yangtze River Economic Zone is conducive to the smooth realization of the total water use control goal. In this paper, Logarithmic Mean Divisia Index (LMDI) is adopted to give consideration to both production water and domestic water. The spatio-temporal difference of water use is decomposed into production intensity effect, industrial structure effect, economic scale effect, domestic intensity effect and population scale effect. The results show that the production water use is the main source of the change of total water use in the Yangtze River Economic Zone and each province, and domestic water use on the increase of total water use is gradually enhanced. Production intensity effect and industrial structure effect are the primary and secondary factors to inhibit the increase of total water use respectively, while economic scale effect and domestic intensity effect are the primary and secondary factors to promote the increase of total water use. Population scale effect is relatively weak in promoting the increase of total water use. Economic growth in agriculture and industry has contributed to the increase in total water use, especially in agriculture. The general decline in the water intensity in agriculture and industry and the decline in the proportion of agriculture added value have contributed to the decline in total water use. Production water use is the main source of spatial difference of total water use among provinces, and the driving factors of spatial difference in total water use between each province and Jiangsu and Chongqing are different. Therefore, all provinces should implement high-quality development, change the mode of economic growth, and focus on saving water in production link and taking into account of living conditions. We will also continue to reduce the intensity of industrial water use，optimize and upgrade the industrial structure, strengthen the management of domestic water quotas and raise people’s awareness of water-saving. The provinces can take Jiangsu and Chongqing as the reference objects and fully explore feasible water-saving paths according to the driving factors of spatial difference of total water use.