In the United States, abolitionism, the movement that sought to end slavery in the country, was active from the colonial era until the American Civil War, the end of which brought about the abolition of American slavery, except as punishment for a crime, through the Thirteenth Amendment to the United States Constitution (ratified 1865).

The anti-slavery movement originated during the Age of Enlightenment, focused on ending the transatlantic slave trade. In Colonial America, a few German Quakers issued the 1688 Germantown Quaker Petition Against Slavery, which marked the beginning of the American abolitionist movement. Before the Revolutionary War, evangelical colonists were the primary advocates for the opposition to slavery and the slave trade, doing so on the basis of humanitarian ethics. Still, others such as James Oglethorpe, the founder of the colony of Georgia, also retained political motivations for the removal of slavery. Prohibiting slavery through the 1735 Georgia Experiment in part to prevent Spanish partnership with Georgia's runaway slaves, Oglethorpe eventually revoked the act in 1750 after the Spanish's defeat in the Battle of Bloody Marsh eight years prior.

During the Revolutionary era, all states abolished the international slave trade, but South Carolina reversed its decision. Between the Revolutionary War and 1804, laws, constitutions, or court decisions in each of the Northern states provided for the gradual or immediate abolition of slavery. No Southern state adopted similar policies. In 1807, Congress made the importation of slaves a crime, effective January 1, 1808, which was as soon as Article I, section 9 of the Constitution allowed. A small but dedicated group, under leaders such as William Lloyd Garrison and Frederick Douglass, agitated for abolition in the mid-19th century. John Brown became an advocate and militia leader in attempting to end slavery by force of arms. In the Civil War, immediate emancipation became a war goal for the Union in 1861 and was fully achieved in 1865.

American abolitionism began well before the United States was founded as a nation. In 1652, Rhode Island made it illegal for any person, black or white, to be "bound" longer than ten years. The law, however, was widely ignored, and Rhode Island became involved in the slave trade in 1700.

An early prominent example of resistance by enslaved people occurred during Bacon's Rebellion in 1676. Occurring in Virginia, the rebellion saw European indentured servants and African people (of indentured, enslaved, and free negroes) band together against William Berkeley because of his refusal to fully remove Native American tribes in the region. At the time, Native Americans in the region were hosting raids against lower-class settlers encroaching on their land after the Third Powhatan War (1644–1646), which left many white and black indentured servants and slaves without a sense of protection from their government. Led by Nathaniel Bacon, the unification that occurred between the white lower class and blacks during this rebellion was perceived as dangerous and thus was quashed with the implementation of the Virginia Slave Codes of 1705. Still, this event introduced the premise that blacks and whites could work together towards the goal of self-liberation, which became increasingly prevalent as abolition gained traction within America.

The first written statement against slavery in Colonial America was prepared in 1688 by members of the Religious Society of Friends. On 18 February 1688, Francis Daniel Pastorius, the brothers Derick and Abraham op den Graeff and Gerrit Hendricksz of Germantown, Pennsylvania, drafted the 1688 Germantown Quaker Petition Against Slavery, a two-page condemnation of slavery, and sent it to the governing bodies of their Quaker meeting. The intention of the petition was to stop slavery within the Quaker community, where 70% of Quakers owned slaves between 1681 and 1705. It acknowledged the universal rights of all people. While the Quaker establishment did not take action at that time, the unusually early, clear, and forceful argument in the petition initiated the spirit that finally led to the end of slavery in the Society of Friends (1776) and in the Commonwealth of Pennsylvania (1780). The Quaker Quarterly Meeting of Chester, Pennsylvania, made its first protest in 1711. Within a few decades the entire slave trade was under attack, being opposed by such Quaker leaders as William Burling, Benjamin Lay, Ralph Sandiford, William Southby, John Woolman, and Anthony Benezet. Benezet was particularly influential, inspiring a later generation of notable anti-slavery activists, including Granville Sharp, John Wesley, Thomas Clarkson, Olaudah Equiano, Benjamin Franklin, Benjamin Rush, Absalom Jones, and Bishop Richard Allen, among others.

Samuel Sewall, a prominent Bostonian, wrote The Selling of Joseph (1700) in protest of the widening practice of outright slavery as opposed to indentured servitude in the colonies. This is the earliest-recorded anti-slavery tract published in the future United States.

Slavery was banned in the colony of Georgia soon after its founding in 1733. The colony's founder, James Edward Oglethorpe, fended off repeated attempts by South Carolina merchants and land speculators to introduce slavery into the colony. His motivations included tactical defense against Spanish collusion with runaway slaves, and prevention of Georgia's largely reformed criminal population from replicating South Carolina's planter class structure. In 1739, he wrote to the Georgia Trustees urging them to hold firm: