There have been substantial conflicts in the human–water relationship in the Huaihe River Basin(HRB). To achieve sustainable economic development without degrading the water environment in the HRB, we develop a three-dimensional water environmental supporting capacity(WESC) model based on water environmental carrying capacity(WECC), water environmental pressure(WEP), and water pollution prevention and control capacity(WPPC). Geographic information systems spatial analysis with the analytical hierarchy process method and dynamic weighted summation is applied. Several proposals for suitable locations for industry and environmental protection strategies for water were presented. The following results were obtained.(1) The spatial differences in WECC are substantial; areas with high-value WECC zones are mainly located along the main stream of the Huaihe River on the south side. WEP is generally high, with an overall low level of pollution prevention and control in the whole HRB. WPPC and WEP show high spatial overlapping due to the fact that areas with higher environmental pollution usually have high level of economic development, and thus have a strong capacity for pollution control.(2) Overall, WESC is moderate in the HRB. In particular, areas with a high WESC value only account for 56.24% of the HRB in 2010. Distinct differences in WESC also exist between areas located in the south compared with in the north of the basin, and areas alongside the downstream region compared with alongside the upstream and midstream regions.(3) Consequently, according to the guidance for industry zoning in the HRB, the areas in the south and alongside the downstream and sub-streams with a low WEP value and high WECC and WPPC, traditional industries should be developed based on strict environmental access and pollution emission standards. While for the areas along the midstream of the HRB and along the whole Yishusi River Basin, which have a high WEP value, industrial restructuring and technological upgrading are suggested. Action should be taken to limit development and protect the environment in the upstream region of the basin, which is a key source of drinking water, in the eastern route along the line of the South-to- North Water Diversion Project, and in the ecologically fragile region alongside the basin. This will ensure good environmental functionality including subsistent provision of clean water, while at the same time satisfying the urgent need to adjust, transform, and upgrade the industrial structure.