This paper analyzed the spatial-temporal pattern evolution of industrial wastewater discharge and its barycenter migration in “Four-city Area in Middle China” from 2006 to 2017, based on Exploratory Spatial Data Analysis (ESDA) method and barycenter migration model. The results showed that the industrial wastewater discharge in “Four-city Area in Middle China” decreased in the studied period, and had obvious spatial differentiation characteristics. Moreover, it showed an evolution law from high to low in the Southwest and from low to high in the Middle East. There was no obvious spatial agglomeration feature in the overall space, but an obvious agglomeration feature in certain local places with low agglomeration in the center and high agglomeration in the surrounding cities. The barycenter of industrial wastewater discharge in “Four-city Area in Middle China” from 2006 to 2017 moved only in the region of 114.38°E-114.95°E east longitude and 29.18°N-29.34°N latitude, and generally moved in the northeast direction, with a total distance of 107.88 km. The barycenter of gross value of industrial output in “Four-city Area in Middle China” generally moved to the northwest, with a total moving distance of 94.39 km, and the moving distance of the barycenter changed little except for 2011 and 2012. From 2006 to 2017, the barycenter of gross value of industrial output in “Four-city Area in Middle China” gradually deviated from the geometric center, while the barycenter centers of industrial wastewater discharge gradually converged to the geometric center, and its moving speed was significantly higher than that of the barycenter of gross value of industrial output.