In national politics, Southerners chiefly sought protection and enlargement of the interests represented by the cotton/slavery system. They sought territorial expansion because the wastefulness of cultivating a single crop, cotton, rapidly exhausted the soil, increasing the need for new fertile lands.   Moreover, new territory would establish a basis for additional slave states to offset the admission of new free states. Antislavery Northerners saw in the Southern view a conspiracy for proslavery aggrandizement.  In the 1830s their opposition became fierce.

An earlier antislavery movement, an offshoot of the American Revolution, had won its last victory in 1808 when Congress abolished the slave trade with Africa. Thereafter, opposition came largely from the Quakers, who kept up a mild but ineffectual protest.  Meanwhile, the cotton gin and westward expansion into the Mississippi delta region created an increasing demand for slaves.

The abolitionist movement that emerged in the early 1830s was combative, uncompromising, and insistent upon an immediate end to slavery. This approach found a leader in William Lloyd Garrison, a young man from Massachusetts, who combined the heroism of a martyr with the crusading zeal of a demagogue. On January 1, 1831, Garrison produced the first issue of his newspaper, The  Liberator, which bore the announcement: "I shall strenuously contend for the immediate enfranchisement of our slave population. ... On this subject, I do not wish to think, or speak, or write, with moderation. ... I am in earnest – I will not equivocate – I will not excuse – I will not retreat a single inch – AND I WILL BE HEARD."

Garrison's sensational methods awakened Northerners to the evil in an institution many had long come to regard as unchangeable. He sought to hold up to public gaze the most repulsive aspects of slavery and to castigate slave holders as torturers and traffickers in human life. He recognized no rights of the masters, acknowledged no compromise, tolerated no delay. Other abolitionists, unwilling to subscribe to his law-defying tactics, held that reform should be accomplished by legal and peaceful means. Garrison was joined by another powerful voice, that of Frederick Douglass, an escaped slave who galvanized Northern audiences.  Theodore Dwight Weld and many other abolitionists crusaded against slavery in the states of the old Northwest Territory with evangelical zeal.

One activity of the movement involved helping slaves escape to safe refuges in the North or over the border into Canada.  The "Underground Railroad," an elaborate network of secret routes, was firmly established in the 1830s in all parts of the North. In Ohio alone, from 1830 to 1860, as many as 40,000 fugitive slaves were helped to freedom. The number of local antislavery societies increased at such a rate that by 1838 there were about 1,350 with a membership of perhaps 250,000.

Most Northerners nonetheless either held themselves aloof from the abolitionist movement or actively opposed it. In 1837, for example, a mob attacked and killed the antislavery editor Elijah P. Lovejoy in Alton, Illinois.  Still, Southern repression of free speech allowed the abolitionists to link the slavery issue with the cause of civil liberties for whites. In 1835 an angry mob destroyed abolitionist literature in the Charleston, South Carolina, post office. When the postmaster-general stated he would not enforce delivery of abolitionist material, bitter debates ensued in Congress.  Abolitionists flooded Congress with petitions calling for action against slavery.  In 1836 the House voted to table such petitions automatically, thus effectively killing them. Former President John Quincy Adams, elected to the House of Representatives in 1830, fought this so‑called gag rule as a violation of the First Amendment, finally winning its repeal in 1844.