Christopher Columbus landed at Môle Saint-Nicolas, in northwest present-day Haiti, on December 6, 1492, during his first voyage. He claimed the island for Spain and named it La Española. Eighteen days later his flagship the Santa María ran aground near the present site of Cap-Haitien. Columbus was forced to leave 39 men, who built a fort named La Navidad (Christmas, or The Nativity). He then sailed east, exploring the northern coast of what is now the Dominican Republic, after which he returned to Spain. He sailed back to America three more times, and was buried in Santo Domingo upon his death in 1506.
After initially friendly relations, the Taínos resisted the conquest. One of the earliest leaders to fight against the Spanish was the female Chief Anacaona of Xaragua, in the southwest, who married Chief Caonabo of Maguana, of the center and south of the island. She was captured by the Spanish and executed in front of her people. Other notables who resisted include Chief Guacanagari, Chief Guamá, and Chief Hatuey, the latter of whom later fled to Cuba and helped fight the Spaniards there. Chief Enriquillo fought victoriously against the Spanish in the Baoruco Mountain Range, in the southwest, to gain freedom for himself and his people in a part of the island for a time.
By the late 1500s, the majority of Taíno people had died from European infectious diseases to which they had no immunity, from mistreatment, suicide, the breakup of family unity, starvation,[15] forced labor, torture, and war with the Spaniards. Most scholars now believe that, among the various contributing factors, infectious disease was the overwhelming cause of the Taíno population decline.[23] The Taíno survived mostly in racially mixed form, and today most Dominicans have Taíno ancestry.
Some scholars believe that Bartolomé de las Casas exaggerated[26] the Indian population decline in an effort to persuade King Carlos to intervene, and that encomenderos also exaggerated it, in order to receive permission to import more African slaves. Moreover, censuses of the time did not account for the number of Indians who fled into remote communities,[24] where they often joined with runaway Africans, called cimarrones, producing zambos. There were also confusing issues with racial categorization, as Mestizos who were culturally Spanish were counted as Spaniards. In addition some Zambos were categorized as black and some Indians as Mulattos.
In 1496 Bartholomew Columbus, Christopher's brother, built the city of Nueva Isabela (New Isabella), now Santo Domingo, in the south of Hispaniola. It was one of the first Spanish settlements (the previous ones had also been on Hispaniola), and became Europe's first permanent settlement in the "New World".
The Spaniards created a plantation economy on Hispaniola, particularly from the second half of the 16th century.[18] The island became a springboard for European conquest of the Caribbean islands, called Las Antillas (The Antilles), and soon after, the American mainland.
For decades, Santo Domingo was the headquarters of Spanish colonial power in the New World. But after the Spanish conquest of the mainland empires of the Aztecs and Incas, the importance of Hispaniola declined and Spain paid less attention to it. French bucaneers settled in the western part of the island, and by the 1697 Treaty of Ryswick, Spain ceded the area to France. With colonial settlement and the development of a plantation economy dependent on slave labor, it grew into the wealthy colony of Saint-Domingue (now Haiti), with four times (500,000 vs. 125,000) as much population as Spanish Santo Domingo by the end of the 18th century. By then, enslaved Africans in Saint-Domingue outnumbered whites and freedmen by nine to one.