In the middle of the fifteenth century, Portuguese traders began to enslave people living in West Africa and transporting them to Madeira to work on the sugar plantations there. The Portuguese began their exploration of the African coast looking for a maritime route to Asia, but soon began to set up trading posts there. Initially, these were used mainly for trading gold, but in the sixteenth century they became dungeons for slaves, as the slave trade expended across the Atlantic to the New World. In the early sixteenth century, the Spanish began to take the first African slaves to the New World. At this stage, what was to become the Middle Passage was not an organized shipping route, and Spanish slave ships normally contained a mixture of people from different races, including some Africans.

The first African slaves to arrive in the North American colonies were brought to Winyah Bay, South Carolina, by Lucas Vázquez de Ayllón in 1526. The vast majority of slaves were sent to the Caribbean and Latin America. About 6–7 % were shipped to North America, and most of these did not come until the eighteenth century. By this time, the slave trade was highly profitable, with millions of slaves being forced to make the crossing, but it began to dwindle in the nineteenth century. The Northern states of the US had all abolished slavery by 1804, and Great Britain passed the Slavery Abolition Act in 1833, freeing the slaves in all British possessions in the Caribbean.