Sixteenth-century Aztec codices preserve a record of at least 13 drought years in central Mexico during the prehispanic and early colonial period. Climate-sensitive tree-ring records recently developed for Mexico confirm 9 of the 13 Aztec drought dates, including the extended drought related to the infamous “famine of One Rabbit” in 1454. One Rabbit is the first year of the 52-yr Aztec calendar cycle, and folklore suggests that famine and catastrophe accompany its return. The Mexican tree-ring data indicate that severe drought occurred immediately before 10 of the 13 One Rabbit years during and before the Aztec era a.d. 882–1558. This relationship between drought and the year preceding One Rabbit is statistically significant and suggests a real climatic origin for the “curse of One Rabbit.”