Climate change is significantly impacting cotton production in the Tarim River Basin. The study investigated the climate change characteristics from 2021 to 2100 using climate change datasets simulated per the Coupled Model Inter-comparison Project phase six (CMIP6) climatic patterns under the Shared Socioeconomic Pathways SSP2-4.5 and SSP5-8.5. The DSSAT-CROPGRO-Cotton model, along with stepwise multiple regression analyses, was used to simulate changes in the potential yield of seed cotton due to climate change. The results show that while future temperatures in the Tarim River Basin will rise significantly, changes in precipitation and radiation during the cotton-growing season are minimal. Seed cotton yields are more sensitive to low temperatures than to precipitation and radiation. The potential yield of seed cotton under the SSP2-4.5 scenario would increase by 14.8%, 23.7%, 29.0%, and 29.4% in the 2030S, 2050S, 2070S, and 2090S, respectively. In contrast, under the SSP5-8.5 scenario, the potential yield of seed cotton would see increases of 17.5%, 27.1%, 30.1%, and 22.6% respectively. Except for the 2090s under the SSP5-8.5 scenario, future seed cotton production can withstand a 10% to 20% deficit in irrigation. These findings will help develop climate change adaptation strategies for cotton cultivation.