Based on the observation data of 127 meteorological stations and historical atmospheric CO2 concentration data in the middle and lower reaches of the Yangtze River from 1981 to 2013, the water demand of rice was simulated with the change of atmospheric CO2 concentration considered or not. The influence of atmospheric CO2 concentration rise on the water demand of rice in the middle and lower reaches of the Yangtze River was analyzed. The results show that, without considering the atmospheric CO2 concentration, the annual average water demand of rice in the middle and lower reaches of the Yangtze River was 400.16 mm, and the spatial distribution was obviously different. The water demand of rice considering atmospheric CO2 concentration decreased by about 1.6% on average compared with that without considering CO2 concentration. For every 1 μmol/mol increase in CO2 concentration, the average water demand of rice in the study area decreased by 0.071 mm. The water demand for irrigation in each sub-basin varies due to different effective rainfall. Considering the change of atmospheric CO2 concentration, the total irrigation water demand for rice in the middle and lower reaches of the Yangtze River decreased by 4.24 km³.