The disjunction of ecological and socioeconomic sciences is one of the main obstructions in current human-natural integrated systems research. Therefore, gridded GIS technology is introduced in an attempt to achieve the spatial flow analysis of water pollution in eco-natural systems. With this unified GIS platform, an input-output table and one-dimensional water quality model are chosen to manifest the spatial economic flows and spatial natural flows of water pollution separately. Finally, the comprehensive effect of the spatial circulation of water pollution in eco-natural systems is assessed. A case study of the framework is carried out in the Changzhou District of Taihu Lake, China, and the main results show the following: (1) COD (chemical oxygen demand) direct emissions represent the characteristics of high intensity and clustering in industrial regions; control unit 8 is the largest secondary emissions unit, representing up to 41.79% of the total, whereas the emissions of the primary industry tend to be low intensity and widespread. (2) The gray virtual water flows from the primary industry to other heavy industries (except the chemical industry) is the main flow type; the transfer amount adds up to 2512 t, and the inter-units with the largest occupation of water environment capacity (WEC) upstream to downstream are 8-9, nearly up to 1548 t. (3) Under the interaction of positive and negative functions of economic flows and natural flows, the final effect of pollution transfer may be offset, environmental degradation or environmental improvement. This study could provide a basis for ecological compensation, environmental exteriority and optimization of industrial structure layouts.