Abstract: Based on the panel data of 108 cities in the Yangtze River Economic Belt from 2009-2018, this paper selects indicators from atmospheric environment, water environment and energy consumption to construct an environmental pollution index, and uses the location quotient index to measure the level of manufacturing agglomeration. On the basis of clarifying the mechanism of the environmental effect of manufacturing agglomeration, this paper uses benchmark regression model and threshold regression model to empirically test the impact of manufacturing agglomeration on environmental pollution in the Yangtze River Economic Belt. The results show that: (1) From 2009 to 2018, the manufacturing agglomeration level in the lower reaches of the Yangtze River Economic Belt was the highest, followed by the middle reaches, and the upper reaches was the lowest. (2) The overall environmental pollution level of the Yangtze River Economic Belt shows a downward trend, and the improvement of urban environmental pollution in the lower reaches is higher than that in the middle and upper reaches. (3) The whole Yangtze River Economic Belt and the middle and lower reaches of the Yangtze River show an “N” curve relationship between manufacturing agglomeration and environmental pollution, which first promotes, then inhibits and then intensifies. However, the manufacturing agglomeration in the upper reaches is still in the stage of aggravating pollution. We should balance the benign relationship between manufacturing agglomeration and environmental pollution, continuously increase the investment in environmental protection science and technology, strictly enforce environmental regulations, and formulate the differentiation policy of manufacturing industry agglomeration in the Yangtze River Economic Belt.