This paper reinterprets the historical development of policy-oriented American expertise about the Middle East. It does so by analyzing the fundamental dilemma posed by the late emergence of the U.S. as a regional power in the 20th century. On the one hand, reconciling U.S. power to anti-colonial nationalism required official and non-state actors to advance exceptionalist claims about the benevolence of American power based on the absence of an imperial past. On the other hand, such claims highlighted a poverty of local knowledge and institutional expertise necessary for carrying out the self-described American missions of developing and democratizing the Middle East. According to the existing historical literature on America's Middle East foreign policy, the U.S. government attempted to address this dilemma by drawing upon the experience of Christian missionaries, knowledge produced by the oil industry, and support for Zionism-as-modernization. On the basis of new research in government archives, private manuscripts, and published sources, however, this paper will show how U.S. experts translated and “Americanized” regional knowledge drawn from other sources, including those derived from Ottoman and British imperial precedents. Such translations occurred with the assistance of European and Middle Eastern interlocutors who portrayed the region’s societies as open fields for U.S.-administered change. The argument focuses on three areas: shifting uses of the Ottoman past by U.S.-based scholars and officials to imagine and map regional development; American-sponsored land reform strategies that drew upon the inheritance of Ottoman- and mandate-era agricultural policies; and adaptation of post-Ottoman, Arab nationalist historiography to justify cold-war strategies of authoritarian modernization. This research offers new perspectives on the relationship between knowledge and power in the U.S. encounter with the Middle East. It not only analyzes the role of the Middle East in producing American exceptionalism but also helps to clarify the nature of the relationship between European Orientalism and post-1945 American social science.