In the Southeast US, El Nino Southern Oscillation (ENSO), climate variability phenomena affect the quantity of water that is available for irrigation. The goals of this study were to determine the effect of upstream surface water withdrawals for irrigation on the quantity of water available for irrigation in downstream areas as a function of the ENSO phase and quantify the watershed area that can be irrigated using water withdrawn from streams in an ecologically sustainable manner. The study was conducted in the Swan Creek watershed (97 km2) located in Limestone County, Alabama, USA. The soil and water assessment tool (SWAT) model was used to simulate stream flows and develop water withdrawal prescriptions. Results indicated that when simultaneous water withdrawals were made at the outlet of each subwatershed throughout the year, on average water withdrawals were sufficient to irrigate 4–16% of the area upstream of withdrawal point depending on stream order. At the watershed outlet, the volume of water available for withdrawal was reduced by 41 and 67% during noncrop growing and crop growing season, respectively, when water withdrawals were made at the outlets of all subwatersheds upstream of the watershed outlet compared with no water withdrawals made upstream of the watershed outlet.