The agricultural area in Egypt is the largest consumer of water and still requires more water to expand. Any changes in Nile water supply due to climate change would threaten the agricultural water productivities, both physical productivity and economic productivity, and the food security in Egypt. The objective of the current paper is to investigate the impacts of Nile supply reduction on the agricultural water productivities and food security in Egypt using the Agriculture Sector Model in Egypt (ASME). The results showed that the reduction in Nile supply will either increase or decrease the areas of different crops, and generally will decrease the total cropped area. Regarding the food security, all indicators refer to a slight decline in the food security progress in terms of reduction of water availability, self-sufficiency of strategic food crops, and net virtual water import. The reduction in Nile supply will also deteriorate the economic situation, which can be confirmed by the reduction in agricultural productivity, consumer-producer surplus, and number of jobs as well as the increase in net imports' value and water marginal value. The current study recommends implementing adaptation measures to efficiently use the available water resources and to increase the agricultural productivity per unit area.