Between 1492 and 1504, Italian explorer Christopher Columbus led four Spanish transatlantic maritime expeditions of discovery to the Americas. These voyages led to the widespread knowledge of the New World. This breakthrough inaugurated the period known as the Age of Discovery, which saw the colonization of the Americas, a related biological exchange, and trans-Atlantic trade. These events, the effects and consequences of which persist to the present, are often cited as the beginning of the modern era.

Born in the Republic of Genoa, Columbus was a navigator who sailed for the Crown of Castile (a predecessor to the modern Kingdom of Spain) in search of a westward route to the Indies, thought to be the East Asian source of spices and other precious oriental goods obtainable only through arduous overland routes. Columbus was partly inspired by 13th-century Italian explorer Marco Polo in his ambition to explore Asia and never admitted his failure in this, incessantly claiming and pointing to supposed evidence that he had reached the East Indies. Ever since, the Bahamas as well as the islands of the Caribbean have been referred to as the West Indies.

At the time of Columbus's voyages, the Americas were inhabited by Indigenous Americans. Soon after first contact, Eurasian diseases such as smallpox began to devastate the indigenous populations. Columbus participated in the beginning of the Spanish conquest of the Americas, brutally treating and enslaving the natives in the range of thousands.

Columbus died in 1506, and the next year, the Americas were named after Amerigo Vespucci, who realized that these continents were a unique landmass. The search for a westward route to Asia was completed in 1521, when another Spanish voyage, the Magellan-Elcano expedition sailed across the Pacific Ocean and reached Southeast Asia, before returning to Europe and completing the first circumnavigation of the world.