Many agricultural water uses crowd the river ecology of the river water, thus leading to irreversible habitat damage. This paper presents an agricultural economic loss calculation model that is based on river ecological basic flow (REBF) protection by introducing a typical crop water requirement coefficient. First, the water balance equation is used according to a set of REBF protection values to compute the agricultural water shortage that results in the REBF. Second, the agricultural water shortage that results in REBF protection and a typical crop water requirement coefficient are used to determine the food production generated by REBF protection. Finally, the loss of food production and the food market prices are used to determine the agricultural economic loss caused by the different protection levels of REBF. A case study of the Weihe River in China is conducted. The calculation model is used to compute the agricultural economic loss on the basis of REBF protection in the Baoji section of the Weihe River, and the change law of the agricultural economic loss that results in different levels of the REBF is discussed. In addition, changes in the canal water use coefficient and the crop structure that affect agricultural economic loss are analyzed. Results show that the spatial and temporal variations in the runoff affect the changes in time and space of the agricultural economic loss. The higher the REBF protection level, the higher the agricultural economic loss. In addition, agricultural economic loss can provide a quantitative basis for reasonable REBF protection. The size of agricultural economic loss helps the government sector in decision-making on REBF protection.