Abstract: Dongjiang Lake is a national nature reserve. With the acceleration of urbanization and industrialization, water resources are becoming increasingly scarce and water environmental pollution is becoming prominent. How to accurately compare and evaluate the water resource utilization status in Dongjiang Lake Basin has become an urgent problem that needs to be solved. Based on the water footprint theory, seven indicators were selected from four perspectives: water footprint structure, water footprint utilization, water footprint safety, and water footprint development. Based on water resources and economic and social development data from 2012 to 2022 in the Dongjiang Lake Basin, the water resource consumption was calculated, and the water resource development and utilization situation was evaluated. The Tapio decoupling model was used to measure the matching status of water footprint and economic and social development in the Dongjiang Lake Basin. The results indicated that the water footprint of the Dongjiang River Basin was mainly based on agricultural and industrial water use, with agricultural water consumption accounting for over 58%. The efficiency of water resource utilization has gradually improved since 2018. The import and export water footprint belongs to the net export type of water resources. The water footprint pressure was between 0.42 and 0.61, and water resource consumption cannot be guaranteed under extreme drought conditions. The average water consumption of urban and rural residents had increased rapidly. The Tapio coefficient showed that from 2012 to 2016, the water footprint and economic development were mainly in a growth-linked state. From 2017 to 2022, the frequency of weak decoupling increased, especially in 2022, when the decoupling coefficient approached the level of −0.44. Research has shown that the Dongjiang Lake Basin has sufficient water resources to meet the needs of regional industrial and agricultural production and residential life, but it is necessary to be vigilant against the impact of the extreme arid climate. At the same time, it is necessary to improve the efficiency of water resource utilization, leverage the advantages of water resources to upgrade regional industrial structure, and develop the "water economy" in combination with water resource advantages.