Columbus set sail from Sanlúcar de Barrameda, Spain, on his third voyage with six ships. This voyage aimed to further explore the lands he had discovered and to alleviate the problems in the colony on Hispaniola.

Columbus reached the island of Trinidad, marking the first time he encountered the mainland of South America. He explored the Gulf of Paria and the Orinoco River delta, realizing that he had discovered a large landmass.

Columbus made landfall on the South American mainland near present-day Venezuela. He believed that this land was part of Asia and that the Orinoco River was a river flowing from the Garden of Eden.

Upon arriving in Hispaniola, Columbus found the colony in a state of chaos. Spanish settlers were in revolt against his rule, and the indigenous population was suffering from disease and exploitation. Columbus struggled to maintain order.

King Ferdinand and Queen Isabella, concerned about the reports of mismanagement and brutality in Hispaniola, appointed Francisco de Bobadilla as governor and judge to investigate Columbus's administration.

Bobadilla, after investigating the situation in Hispaniola, ordered the arrest of Columbus and his brothers, Diego and Bartholomew. They were imprisoned and sent back to Spain in chains, accused of tyranny and incompetence. This event marked a significant low point in Columbus's career.

Upon arrival in Spain, Columbus was released from prison, but he lost his titles and authority as governor. He was able to convince King Ferdinand and Queen Isabella to grant him one more voyage, but he never regained his former status.