The Euphrates River flowed through the Ottoman Empire’s eastern frontier, where Ottoman authorities struggled against various enemies, foreign and domestic. Relying mainly on Ottoman and Arabic sources, this paper will examine the Euphrates in the 18th century as an Ottoman frontier river. It seeks to demonstrate that fluvial dynamics and the Ottoman struggle against mobile pastoral groups in the Empire’s eastern frontier were closely intertwined, and they influenced and shaped each other. Particular emphasis will be given to the Ottoman conflict with the Khaza’il tribal confederation on the banks of the Middle Euphrates. The position of the Euphrates as a frontier river constrained Ottoman efforts to tame it and bring it under close state control. Without a comprehensive irrigation infrastructure and systematic flood control measures, the Euphrates often generated massive floods and created marshlands on its floodplains. In the Ottoman struggle against mobile pastoral groups, Euphrates floods and marshes were not neutral. Rather, they were the natural allies of mobile pastoralists and the natural enemies of grain farmers and the Ottoman provincial administration in Baghdad. Ottoman policy to deal with the challenge posed by mobile pastoral groups in the Empire’s eastern frontier had a transformative impact on the Euphrates River. Throughout the 18th century, Ottoman officials pursued an environmental warfare to defeat their pastoral foes. They built massive dams and drained the marshes of their enemies in order to make the landscape of the Middle Euphrates more legible and facilitate state interventions and control in the region. Such measures had a profound impact on the Euphrates and induced it to follow a more westerly course since the late 18th century. By highlighting the relationship between the Euphrates River and Ottoman frontier politics in the 18th century, this paper aims to demonstrate that humanity and nature engage in an intimate dialogue. This dialogue has significant consequences for humans and the ecosystems they interact with on a daily basis and should not be placed in the background of human affairs.