This study was conducted to investigate weed infestations of cotton (Gossypium hirsutum) fields in the region of Tarim River. Forty‐nine species among 17 families were identified in these cotton fields, and 24 of them were annuals. The eight dominant weed species in the cotton fields of Tarim River basin included Chenopodium glaucum, Solanum nigrum, Chenopodium album, Chenopodium hybridum, Bolboschoenus planiculmis, Sonchus arvensis, Phragmites australis, and Mulgedium tataricum. The number of weed species in the Aksu River tributary area, Yeerqiang River tributary area, and the upper and lower reaches of the Tarim River reached 29, 36, 35, and 33, respectively. Twenty species were found widely distributed among each basin. The dominant weeds in the cotton fields in the Aksu River basin and upper reaches of the Tarim River were S. nigrum and C. glaucum, those in the cotton fields in the Yarkand River basin included C. album and C. hybridum, and those in the cotton fields in the lower reaches of the Tarim River were C. glaucum and C. album. Notably the 20 common surveyed species of C. glaucum, S. nigrum, C. album, C. hybridum, B. planiculmis, S. arvensis, P. australis, M. tataricum, and others, could pose a serious challenge to regional crop production if not adequately controlled. As such, each cotton field should adopt a suitable weeding scheme with strengthened weed monitoring according to the local conditions, especially the weed distribution area characteristics.