On Christmas Day 1521, in the Spanish colony of Santo Domingo, the first recorded slave revolt in the Americas occurred. A group of African, likely Wolof, slaves came together with native Indians led by the Taíno cacique Enriquillo to assert their independence. Beyond being the first slave revolt in the Americas, it was also one of the most important moments in Colonial American history because it was the first known instance when Africans and Indians united against their Spanish overlords in the Americas. Little scholarship exists that focuses on the event, and what does exist concentrates on either the Indian or the African revolt without linking the two events. By overlooking the revolt and its origins, Latin American historiography perpetuates the portrayal of Española as a stepping stone or “antechamber” to the conquest of Mexico or Peru, only focusing on the initial discovery by Christopher Columbus before leaving the Caribbean behind. This essay addresses these silences by carefully examining the evolution of colonial society on Española using sources found in the Archivo General de Indias and recent archaeological studies. Among the themes I analyze in my article are the scope and meaning of the early indigenous slave trade; the greater social, political, and cultural impact of the Caribbean slave trade from 1500 to 1530; the factors that prompted both the Indians and Africans to revolt; and the roles played by the various religious groups on the island. This essay will serve as a case study of an event when Africans and Indians joined against a common enemy, thereby gaining their own agency and power. In the end, this study will be applicable to the larger Spanish colonial experience of cultural hybridization and the African and Indian diasporas.