Santo Domingo became the first permanent European colony and city in the Americas (1495–1496). As the local Taínos encountered waves of Spanish invaders after the arrival of Christopher Columbus, colonial Santo Domingo and the island of Hispaniola (a region called Ayiti or Quisqueya by its then inhabitants) sank into a series of foreboding firsts of European colonialism in the Americas. Santo Domingo was the first site of mass indigenous forced labor, die-offs, and coerced conversions. It was home to the first boom-and-bust cycles in both gold and sugar, was a base for Spanish expansion across the region, and the location of initial African enslavement and slave revolts in the Western Hemisphere. Though Spanish profits surged from other parts of their sprawling empire in the Americas, Santo Domingo remained a hub of governance and religiosity given the presence of the Audiencia and Arzobispado in the city. Santo Domingo in the Age of Revolutions again became pivotal to salient points of dawning political modernity due to its frontier on Hispaniola with the revolutionary French (after 1789) and the even more radical Haitian state (after 1804). After the start of the Haitian Revolution (1791) in particular, Dominicans and Spanish officials were at the forefront of debates over abolition, secularism, and republicanism. In the ensuing seventy years of near-constant political turmoil, slaves gained emancipation in neighboring Saint-Domingue (1793), the French Republic occupied Santo Domingo (1802–1809), and an elite and moderate Dominican independence project (1821) was supplanted by Haitian annexation with popular appeal (1822). Despite efforts at decolonization and the establishment of the Dominican Republic (1844), remnants of Hispanic nostalgia resurfaced in elite politics to define Dominicans as protectors of Spanish culture. Spanish recolonization (1861–1865) prompted mass Dominican dissent over the fear of reenslavement and ended in the reestablishment of an independent Dominican Republic with support of regional neighbors, like Haiti. In more-recent years, scholarship has moved beyond dated, top-down accounts of the colonial era that often serviced elite Dominican nationalism, and in the mid-20th century the Trujillo dictatorship’s antihaitianismo and hispanismo, which lingered through the many years of Balaguer and beyond. This scholarly turn nuances our understandings of Dominican race and slavery, revolutionary connectivity, and solidarity with Haitians, which in sum supplement persistently relevant works related to political, institutional, economic, and military histories of the Spanish Empire. Scholarship on colonial Santo Domingo could still benefit from gender studies and environmental histories.