The anti-American inclination of the Islamic Republic of Iran’s foreign policy-making is well established, and the bitter aspects of the two nation’s history well known. However, to assert a simple causal relationship between history and foreign-policy structure portrays the Islamic Republic’s anti-Americanism as inevitable, eternal and unrelated to actors’ agency. This article disputes this simple structural understanding by drawing on Greener’s method of applying path-dependency theory to political science. We first identify the ideas and structure of revolutionary Iran, benefiting in particular from the complementary insights of postcolonial theory. Following, we examine US policy choices in the Islamic Republic’s formative period of 1978–79—specifically those related to human rights, the shah and direct US intervention—and how these were perceived and acted upon in Tehran. Our findings indicate that American actions and Iranian decisions both influenced the establishment of a path-dependent process of perception and perpetration that continues until today. Successive Iranian governments have asserted that America ignores Iranian’s human rights, supports their enemies, and pursues direct intervention, while successive US government actions, motivated by Iranian counter-actions, have generated ample evidence to validate such claims. This can explain how a spiral of distrust emerged between the two nations.