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According to his biographer Robert Remini, Adams was initially not an abolitionist. Rather, he believed that the end of slavery would come either by civil war or the consent of the slave South, not through the work of abolitionists. The turning point in his thinking came about during the debate on the Missouri Compromise in 1820. Adams broke with his former friend John C. Calhoun, who became the most outspoken national leader in favor of slavery. The two men became bitter enemies. Adams vilified slavery as a terrible evil and preached total abolition, while Calhoun argued that the right to own slaves had to be protected from interference from the federal government to keep the nation alive. Adams said slavery contradicted the principles of republicanism, while Calhoun said that slavery was essential to American democracy, because it made all white men equal. Both men pulled away from nationalism, and started to consider dissolution of the Union as a way of resolving the slavery issue.
Adams believed that if the South formed a new nation, it would be torn apart by an extremely violent slave insurrection. In a remarkable vision of what was to come, Adams predicted that if the slave states formed a new nation and went to war with the free states, the president of the United States would use his war powers to abolish slavery.
In Congress. Adams became a champion of free speech, demanding that petitions against slavery be heard. Congressional leaders devised a "gag rule" that said they could not be heard. Adams crafted ways to circumvent it, leading to the following motion of censure proposed by Congressman Waddy Thompson:
Resolved, that J.Q. Adams, a member from the State of Massachusetts, by his attempt to introduce into this House a petition of slaves for the abolition of slavery in the District of Columbia, committed an outrage on the rights and feelings of a large portion of the people of the Union, a flagrant contempt on the dignity of this House; and by extending to slaves a privilege only belonging to freemen, directly incites the slave population to insurrection; and that the said member be forthwith called to the bar of the House, and censured by the Speaker.
Adams took advantage of his right to defend himself in front of the members to deliver days of prepared and impromptu remarks against slavery and in favor of abolition. He spoke against the slave trade and the ownership of slaves. Adams went so far as to suggest the dissolution of the Union on the grounds that to remain whole would mean supporting the institution of slavery and the views of southern slaveholders. As others continued to attack him and call for his censure, Adams continued to debate the issues of slavery and the evils of slaveholding. Adams had cleverly neutered the gag rule by debating slavery on the House floor in the moments he was allowed to rise in his defense against the threat of censure. On February 7, 1842, the United States House of Representatives voted 106 to 93 to table the motion to censure Representative Adams.
In 1841, Adams representing the African defendants in United States v. The Amistad Africans in the Supreme Court of the United States. He successfully argued that the Africans, who had seized control of a Spanish ship on which they were being transported illegally as slaves, should not be extradited or deported to Cuba (a Spanish colony where slavery was legal) but should be considered free. Under President Martin Van Buren, the government argued the Africans should be deported for having mutinied and killed officers on the ship. Adams won their freedom, with the chance to stay in the United States or return to Africa. Adams made the argument because the U.S. had prohibited the international slave trade, although it allowed internal slavery. He never billed for his services in the case. His closing speech was directed not only at the justices of the court hearing the case, but to the larger national audience he was able to reach through the press, to remind them of the evils of slavery.
Adams repeatedly spoke out against the organized political power of the slave owners who dominated all the southern states and their representation in Congress. He strongly opposed the annexation of Texas and the Mexican War, which he saw as an unjust war which was part of a "conspiracy" to extend slavery.
On February 21, 1848, the House of Representatives was voting on a relatively non-controversial motion honoring US Army officers who served in the Mexican-American War. Adams was firmly opposed to the motion because he saw it as giving legitimacy to a war that the nation should never have entered into. When the rest of the house voted 'aye', Adams cried out, 'No!' Immediately thereafter, he collapsed from a massive cerebral hemorrhage. Two days later, on February 23, he died with his wife and son at his side in the Speaker's Room inside the Capitol Building in Washington, D.C. His last words were reported to have been, "This is the last of Earth. I am content."