Eupatorium adenophorum has caused tremendous ecological and economic losses in China since the 1940s. Although a great deal of money has been expended on the prevention and control of the weed, the situation is still deteriorating. To identify its crucial environmental constraints, an ecological niche factor analysis was employed. The distribution of the weed was predicted by the maximum entropy model. The results indicate that the temperature in winter is more influential than that in other quarters of a year, and the maximum temperature in March restricts the spread of E. adenophorum most. Currently, the weed is mainly distributed in four provinces of southwest China. From the present to the 2080s, the center of L3, which has a potential distribution probability of 0.7 to 1.0, will move 53 km to the southwest. Accordingly, the area of L3 will expand by 16.04%. To prevent its further expansion, we suggest differentiating the prevention and control measures according to the potential distribution levels predicted. Meanwhile, the integration of various means of removal and comprehensive utilization of E. adenophorum is highly encouraged. Additionally, precautions should be taken in regions that have not yet, or have been only slightly, invaded by the E. adenophorum.