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Slavery in the United States existed as a legal institution from the early years of the colonial period; it was firmly established by the time the United States sought independence from Great Britain in 1776. However, by 1804, all states north of the Mason and Dixon Line had either abolished slavery outright or passed laws for the gradual abolition of slavery. In 1787 Congress prohibited slavery in the Northwest Territory, after a proposal by Thomas Jefferson to abolish it in all the territories failed by one vote. However, slavery gained new life in the South with the cotton industry after 1800, and expanded into the Southwest. The nation was polarized into slave and free states along the Mason-Dixon Line, which separated Pennsylvania and Maryland. The international import or export of slaves became a crime under U.S. and British law in 1808. By the 1850s the South was vigorously defending slavery and its expansion into the territories. In the North a small number of abolitionists denounced it as sinful, and a large number of anti-slavery forces rejected it as detrimental to the rights of free men.[citation needed] Compromises were attempted and failed, and in 1861 eleven slave states broke away to form the Confederate States of America, leading to the American Civil War. The federal government in 1862 made abolition of slavery a war goal. In 1863 President Abraham Lincoln freed slaves in the rebellious southern states through the Emancipation Proclamation. The Thirteenth Amendment, taking effect in December 1865, permanently abolished slavery throughout the entire United States, including the Border states, such as Kentucky, which still had about 50,000 slaves, and the Indian tribes.

From the 16th to the 19th centuries, an estimated 12 million Africans were shipped as slaves to the Americas.(see Slavery in the Americas) The great majority went to the sugar plantations of the West Indies or Brazil, where mortality was high. About 645,000 were brought to what is now the United States. By the 1860 United States Census, the slave population in the United States had grown to four million. Of all 1,515,605 families in the 15 slave states, 393,967 held slaves (roughly one in four), amounting to 8% of all American families.

Slave labor in the form of house servants was in demand in the North (before 1800) and in southern cities. But the great majority of slaves worked on plantations or large farms, where good-quality soil and climate made for lucrative cash crops using labor-intensive cultivation, especially rice, tobacco, sugar and, after 1800, chiefly on cotton. By 1860 most slaves were held in the Deep South, where they were engaged in a work-gang system on large plantations; two-thirds worked in cotton. In small operations they worked side by side with their owners. In large plantations they were directed by white paid overseers.

Under the system that became chattel slavery (ownership of a human being, and of his/her descendants), a racial element was critical: slaves were blacks of African descent and owned, almost universally, by whites of European descent. Children of slave mothers always became slaves themselves. Freedom was only possible by running away (which was difficult and illegal to do), or by manumission by the owner, which was frequently regulated, and sometimes prohibited, by applicable law.

In the earliest era of chattel slavery, much work was also organized under a system of bonded labor known as indentured servitude. This typically lasted for several years for both poor Europeans and Africans alike. Europeans paid with their labor for the costs of transport to the colonies. They contracted for such arrangements because of poor economies in their home countries. Between 1680 and 1700, as fewer Europeans migrated to the colonies, planters began to import more Africans as slaves. Recognizing the importance of slavery, the House of Burgesses in Virginia enacted a new slave code in 1705; it brought together a variety of legislation and added new provisions that embedded the principles of white supremacy in the law. By the early 18th century, colonial courts and legislatures had racialized slavery, essentially creating a caste system in which slavery applied nearly exclusively to Black Africans and people of African descent, and occasionally to Native Americans.

Slaveholders and the commodities of the South had a strong influence on American politics: "in the 72 years between the election of George Washington and the election of Abraham Lincoln, 50 of those years [had] a slaveholder as president of the United States, and, for that whole period of time, there was never a person elected to a second term who was not a slaveholder." Slavery was a contentious issue in the History of the United States from the 1770s through the 1860s, becoming a topic of debate in the drafting of the Constitution (with the slave trade protected for 20 years and slaves being counted toward Congressional apportionment); a subject of Federal legislation, such as the criminal ban on the international slave trade in 1808 and the passage of the Fugitive Slave Act of 1850; and a subject of landmark US Supreme Court cases, such as the Dred Scott decision of 1857.

Slaves resisted the institution through rebellions and non-compliance, and escaped it through travel to non-slave states and Canada, facilitated by the Underground Railroad. Advocates of abolitionism engaged in moral and political debates, and encouraged the creation of Free Soil states as Western expansion proceeded. Slavery was a principal issue leading to the American Civil War. After the Union prevailed in the war, slavery was made illegal throughout the United States with the adoption of the Thirteenth Amendment to the United States Constitution. In the South, freed slaves had second class legal and economic status after the 1870s through sharecropping, and Jim Crow laws to enforce racial segregation, white supremacy and legal disfranchisement that persisted into the mid-1960s.