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The high environmental pollution load caused by the massive pollutant emissions and the accumulation of endogenous and cross-regional pollution has become an important obstacle to the current ecological civilization construction in the Yangtze River Economic Belt (YREB) in China. Taking the YREB as an example, by using four environmental pollutant emission indicators, including chemical oxygen demand (COD), ammonia nitrogen (NH3-N), sulfur dioxide (SO2), and nitrogen oxides (NOx), this paper established an environmental pollution load index (EPLI) based on the entropy-based measurement. Moreover, the Spatial Durbin Model was used to quantitatively analyze the drivers and spatial effects of environmental pollution load. Finally, specific scientific references were provided for formulating environmental regulations of pollution source control in the YREB. The results showed that: 1) During 2011–2015, the EPLI in the YREB was reduced significantly and the environmental pollution load increased from upstream to downstream. Among them, the pollution load levels in the Upper Mainstream subbasin, Taihu Lake subbasin, and Lower Mainstream subbasin were the most prominent. 2) The environmental pollution load situation in the YREB was generally stable and partially improved. High load level areas were mainly concentrated in the Yangtze River Delta Region and the provincial borders in upstream, midstream, and downstream areas. The high load level areas already formed in Chengdu and Chongqing were also the key regulatory points in the future. 3) The degree of local environmental pollution load was apparently affected by the adjacent cities. The population size, industrialization level, and the fiscal decentralization not only drove the increase of the local environmental pollution load level, but also affected the adjacent areas through the spatial spillover effects. The land development intensity mainly drove the increase in the local EPLI in the YREB. While factors such as economic development level and agricultural economic share could only act on the environmental pollution load process in adjacent cities. 4) According to the differentiation characteristics of drivers of each city, the YREB was divided into seven zones based on k-medoids cluster method, and targeted zoning control policy recommendations for alleviating environmental pollution load in the YREB were proposed. [ABSTRACT FROM AUTHOR]