Parthenium weed (Parthenium hysterophorus L.) is among the most noxious invasive alien plant species, which can pose a threat to agro- and native-ecosystems. Despite potential parthenium infestation risks at the south-western regions of the Ganges–Brahmaputra floodplains of Bangladesh, no studies exist that document parthenium infestation. Using field surveys and a maximum entropy (Maxent) modelling approach, the present study tries to address the problem in the concerned region comprised of five Districts: Jashore, Jhenaidah, Chuadanga, Meherpur, and Khustia. The results revealed high infestation in the Jashore, Jhenaidah, and Chuadanga Districts, mainly along roadsides, in grasslands, and in fallow and cropped fields. The greatest abundance of the weed (ca. 30 plants m−2) occurred at the Indian border area, suggesting cross-border spreading, possibly through the linking road systems. Furthermore, we found that under both low and high emissions scenarios (Representative Concentration Pathways 2.6 and 8.5), parthenium weed suitability areas were likely to expand, suggesting an increased threat to the agro-ecosystems of Bangladesh. The present study is the first attempt to survey and model potential parthenium weed distribution affecting one of the major hubs of agricultural production in Bangladesh. The findings of this study can help land managers to make judicious decisions towards the future management of these agro-ecosystems.