The relation between Syria and Turkey transformed from enmity in the 1990s to détente in the early 2000s, grew into amity after the rise to power of the Turkish Justice and Development Party (AKP, Adalet ve Kalkinma Partisi) in 2002, and reverted to enmity in the aftermath of the Arab Spring. This paper suggests that a combination of structural and identity-based factors, at regional and domestic levels, induced the collapse of the decade-long amity. This paper builds on the notion of a “structure-identity nexus”; and determines the orientation of foreign policy outcomes from the 1990s until 2011. The discussion outlines the merits of a hybrid theoretical perspective which draws on two rival traditions, realism and constructivism. The structure-identity framework explains the double transformation in the relationship, considering the return to inter- and intra-state conflict in 2011. The research draws on extensive primary and secondary sources, as well as interviews carried out with key figures. In addition to the relationship between Syria and Turkey, the structure-identity nexus provides potential broader explanations that fuel the shift from amity to enmity in the complex network of states found in the Middle East.