To clarify the key driving factors of the occurrence of poisonous and harmful weeds in grasslands and their responses to anthropogenic disturbances, distribution data of five poisonous and harmful weeds in grasslands, namely Sophora alopecuroides, Aconitum leucostomum, Xanthium spinosum (spiny cocklebur), Rumex thianschanicus, and Peganum harmala, were collected in the Ili River Valley, Xinjiang, from 2022 to 2024. By integrating factors such as climate, topography, soil, and human footprint, the Maximum Entropy (MaxEnt) model was employed to investigate the key factors influencing the occurrence of poisonous and harmful weeds in grasslands and the impact of human activities on their occurrence trends. The results indicated the following: (1) There were differences in the key factors influencing the occurrence of the five poisonous and harmful weeds in grasslands. Overall, temperature, grassland type, soil basic saturation, NDVI, and distance to roads had more pronounced impacts. (2) Under anthropogenic disturbances, the potential occurrence areas, in descending order, were as follows: Xanthium spinosum (28,300 km2), Rumex thianschanicus (24,300 km2), Sophora alopecuroides (22,400 km2), Aconitum leucostomum (18,800 km2), and Peganum harmala (14,400 km2). (3) Anthropogenic disturbances increased the potential occurrence areas of Sophora alopecuroides, Xanthium spinosum, and Peganum harmala, while reducing those of Aconitum leucostomum and Rumex thianschanicus. Additionally, it led to a decrease in the area of multi-species overlap of poisonous and harmful weeds in grasslands. The research findings can provide a reference basis for the scientific prevention and control of poisonous and harmful weeds in the grasslands of the Ili River Valley.