Long-term unsustainable use or overexploitation of groundwater resource have led to different degree of water table declining from arid to even humid regions across the globe. The Lower Mississippi River alluvial plain (refers to MS Delta) in Mid-South US, for example, in subtropical humid Mississippi state, is a watershed where groundwater level has declined the most in the United States. It is even worse than any states and watersheds in the arid and semiarid regions such as Mid-West and western USA. Approximately 35 million cubic meter per day of water from the alluvial aquifer in MS Delta are withdrawn for irrigation, as a result, groundwater level has declined > 6.5 m since 1970, which threaten the sustainability of irrigated agriculture in this region. Surface water as an alternative irrigation source must be taken for sustainability of irrigated agriculture in the region. The objectives of the study were to: 1) determine the total amount of available surface water resources and its temporal and spatial variation in MS Delta; 2) simulate groundwater recharge as affected by ET based and soil moisture based full irrigation schemes using all groundwater and different percentages of surface and ground water. The coupled SWAT (Soil and Water Assessment Tool)-MODFLOW (Finite Difference groundwater model) will be employed to investigate changes in groundwater level and storage for the scenarios as mentioned above under long-term historical weather conditions and projected future 50-100 years of climate change conditions. The average loss of groundwater each year will be estimated under conventional irrigation schedules and methods, ET based and soil moisture based schedule using all groundwater and different percentages of surface water and groundwater. The amounts of weekly groundwater use for cotton, corn and soybean irrigation that could be replaced by surface water will be determined. Results will reveal the decrease in groundwater storage due to conventional irrigation in crop season. It is promising that the sustainable groundwater management practices using either ET or soil moisture based groundwater irrigation scheduling, along with the conjunctive use of surface water, will be identified for mitigation of declining water tables under future climate changes in the Mid-South United States.