quality:correction, structural:scholar_edition
16th century: gold, sugar and pirates

Gold mining using forced indigenous labor began early on Hispaniola. Miguel Díaz and Francisco de Garay discovered large gold nuggets on the lower Haina River in 1496. These San Cristobal mines were later known as the Minas Viejas mines. Then, in 1499, the first major discovery of gold was made in the cordillera central, which led to a mining boom. By 1501 Columbus's cousin, Giovanni Colombo, had discovered gold near Buenaventura. The deposits were later known as Minas Nuevas. Two major mining areas resulted, one along San Cristobal -Buenaventura, and another in Cibao within the La Vega -Cotuy- Bonao triangle, while Santiago de los Caballeros, Concepción, and Bonao became mining towns. The gold rush of 1500–1508 ensued, and Ovando expropriated the gold mines of Miguel Díaz and Francisco de Garay in 1504, as pit mines became royal mines for Ferdinand II of Aragon, who reserved the best mines for himself, though placers were open to private prospectors. King Ferdinand kept 967 natives in the San Cristóbal mining area, supervised by salaried miners.

Under the royal governor Nicolás de Ovando, the indigenous people were forced to work in the gold mines. By 1503, the Spanish Crown legalized the allocation of private grants of indigenous labor to particular Spaniards for mining through the encomienda system. Once the indigenous were forced into mining far from their home villages, they suffered hunger and other difficult conditions. By 1508, the Taíno population of about 400,000 was reduced to 60,000, and by 1514, only 26,334 remained. About half resided in the mining towns of Concepción, Santiago, Santo Domingo, and Buenaventura. The repartimiento of 1514 accelerated emigration of the Spanish colonists, coupled with the exhaustion of the mines. The first documented outbreak of smallpox, previously an Eastern hemisphere disease, occurred on Hispaniola in December 1518 among enslaved African miners. Some scholars speculate that European diseases arrived before this date, but there is no compelling evidence for an outbreak. The natives had no acquired immunity to European diseases, including smallpox. By May 1519, as many as one-third of the remaining Taínos had died. In the century following the Spanish arrival on Hispaniola, the Taíno population fell by up to 95% of the population, out of a pre-contact population estimated from tens of thousands to 8,000,000. Many authors have described the treatment of Tainos in Hispaniola under the Spanish Empire as genocide.

Sugar cane was introduced to Hispaniola by settlers from the Canary Islands, and the first sugar mill in the New World was established in 1516, on Hispaniola. The need for a labor force to meet the growing demands of sugar cane cultivation led to an exponential increase in the importation of slaves over the following two decades. The sugar mill owners soon formed a new colonial elite.

The first major slave revolt in the Americas occurred in Santo Domingo during 1521, when enslaved Muslims of the Wolof nation led an uprising in the sugar plantation of admiral Don Diego Colon, son of Christopher Columbus. Many of these insurgents managed to escape where they formed independent maroon communities in the south of the island.

Beginning in the 1520s, the Caribbean Sea was raided by increasingly numerous French pirates. In 1541, Spain authorized the construction of Santo Domingo's fortified wall, and in 1560 decided to restrict sea travel to enormous, well-armed convoys. In another move, which would destroy Hispaniola's sugar industry, in 1561 Havana, more strategically located in relation to the Gulf Stream, was selected as the designated stopping point for the merchant flotas, which had a royal monopoly on commerce with the Americas. In 1564, the island's main inland cities Santiago de los Caballeros and Concepción de la Vega were destroyed by an earthquake. In the 1560s, English privateers joined the French in regularly raiding Spanish shipping in the Americas.