The Euphrates River is mentioned as one of the four river-heads originating from a river that flowed out of Eden and divided within the Garden. Alongside the Tigris, the Euphrates is recognized in modern geography, leading many to assume that the Garden of Eden, or the larger region of Eden, was located in Mesopotamia. This assumption is partly based on the presence of these two rivers in the area and the fact that post-Flood civilization began in Babylon. However, the catastrophic nature of the Flood likely altered the pre-Flood geography significantly, making it uncertain whether the Tigris and Euphrates mentioned in Genesis are the same as those known now. It is possible that Noah's descendants named these rivers after their pre-Flood counterparts, casting doubt on the reliability of modern topographical maps for identifying the exact location of Eden.

In the ancient context, the Euphrates River holds significant meaning as a boundary marker for the land promised to Abraham's descendants, as outlined in Genesis 15. This vast territory stretches from a small wadi often identified as the Brook of Egypt to the banks of the Euphrates, encompassing a region that extends into eastern Turkey, and includes parts of Syria, Lebanon, and Iraq. Though Israel never fully controlled this expansive area, even during the reigns of David and Solomon, the Euphrates stands as a defining northern and southeastern limit of the promised land, symbolizing the extensive borders that God intended for His people.