Water is the most important component of agriculture production, especially during the dry seasons when all water sources are scarce yet water needs are very high. The Mekong River Delta in Vietnam is the largest agricultural and aquacultural region in the country where about half of the Delta’s land area is used for rice and upland crop cultivation. One key strategy to address the regional water utility problem is to estimate the net water requirement during the dry seasons. The needs for irrigation water discharge for rice and other upland crops during the dry seasons of the Delta were quantified using the Penman-Monteith equation for estimating reference crop evapotranspiration along with the CROPWAT model for calculating crop irrigation water requirements. In general, the total water taken from the Mekong River flow for irrigation requirements should be approximately 2,300-2,600 m3/s for normal yields in the current agriculture areas and under local cultivation conditions. Water diversion and upstream hydropower projects are challenging tasks, especially in the context of climate change, to satisfy the water needs for agricultural irrigation in the near future. All water stakeholders among the neighbouring countries that rely on the Mekong River must adjust their regional water-use planning as one of the mitigation solutions for the seasonal drought crisis.