Turkey has long been a key U.S. ally, though the partnership has fluctuated. The relationship between the two countries can be characterized as strategic, transactional, and model-dependent, contingent upon circumstances, geopolitical considerations, systemic shifts, Turkey’s domestic dynamics, regime priorities, identity issues, and security threats. Within this context, anti-Americanism in Turkey has evolved due to the ideological orientations of governments, nationalist sentiments, divergent interests, and security concerns. This complexity makes defining the concept challenging. Anti-Americanism reflects broader anti-Western sentiments prevalent in Turkey. Despite being a NATO member since 1952 and historically adopting Western political, cultural, and economic models, many Turks perceive Western countries, particularly the United States, as threats to national sovereignty and cultural identity. Moreover, turbulence in the international system has altered geostrategic interests and patterns of convergence. Accordingly, this chapter evaluates the historical connections, key turning points, fundamental drivers, and challenges in Turkey–U.S. relations to clarify the extent and depth of anti-American sentiment.