Columbus embarked on his second voyage from Cádiz, Spain, with a much larger fleet consisting of 17 ships and over 1,200 men. This expedition was aimed at establishing a permanent colony and exploiting the resources of the newly discovered lands.

Columbus and his fleet explored and named several new islands in the Caribbean, including Dominica, Guadeloupe, Montserrat, Antigua, and Puerto Rico. These discoveries expanded Spain's territorial claims in the region.

Upon returning to Hispaniola, Columbus found that La Navidad, the fort he had left behind, had been destroyed and all the Spanish settlers had been killed by the indigenous Taíno people. This event marked the beginning of increased conflict between the Europeans and the native populations.

Columbus established a new settlement called La Isabela on the northern coast of Hispaniola. This became the first permanent European settlement in the Americas. However, the colony faced numerous challenges, including disease, food shortages, and internal conflicts.

Columbus led expeditions to explore the interior of Hispaniola in search of gold and other resources. He imposed a system of tribute on the indigenous population, forcing them to provide gold or other goods. This system led to widespread abuse and exploitation.

Columbus returned to Spain, leaving his brothers, Bartholomew and Diego, in charge of the colony. He faced criticism for his administration of the colony and the lack of significant wealth generated. However, he remained determined to prove the value of his discoveries.