The Compromise of 1850 is introduced into Congress by Henry Clay as an omnibus bill designed to settle disputes arising from the conclusion of the Mexican War. It passes after Stephen Douglas divides the bill into several parts: California enters the Union as a free state; the slave trade (but not slavery) is abolished in Washington D.C.; the fugitive slave law is strengthened; and the Utah and New Mexico Territories are opened to slavery on the basis of popular sovereignty (allowing territorial voters to decide the issue without federa linterference).

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Kansas-Nebraska Act: In an attempt to spur population growth in the western territories in advance of a transcontinental railroad, Stephen Douglas introduces a bill to establish the territories of Kansas and Nebraska. In order to gain Southern support, the bill stipulates that slavery in the territories will be decided by popular sovereignty. Thus the Kansas-Nebraska Act repeals the Missouri Compromise ban on slavery north of 36 30' in the lands of the Louisiana Purchase.

Ostend Manifesto: The U.S. ministers to Britain, France, and Spain meet in Ostend, Belgium. They draft a policy recommendation to President Pierce, urging him to attempt again to purchase Cuba from Spain and, if Spain refuses, to take the island by force. When the secret proposal, called the Ostend Manifesto, is leaked to the press, it creates an uproar since Cuba would likely become another slave state.

On May 24, Virginia fugitive slave Anthony Burns is captured in Boston and returned to slavery under the provisions of the Fugitive Slave Act. Fifty thousand Boston residents watch his transport through the streets of the city in shackles. A Boston church raises $1500 to purchase his freedom and Burns returns to the city in 1855, a free man.

On May 30, the Kansas-Nebraska act is passed by Congress. The act repeals the Missouri Compromise and permits the admission of Kansas and Nebraska territories to the Union after their white male voters decide the fate of slavery in those territories.

Slavery is abolished in Peru and Venezuela.

The Republican Party is formed in the summer in opposition to the extension of slavery into the western territories.

The Massachusetts Legislature outlaws racially segregated schools.

The Caning of Charles Sumner: Senator Charles Sumner delivers a stinging speech in the U.S. Senate, "The Crime against Kansas," in which he attacks slavery, the South, and singles out his Senate colleague, Andrew Butler of South Carolina, for criticism. In retaliation, Butler's nephew, Congressman Preston Brooks of South Carolina, attacks Sumner with a cane while the Massachusetts senator is seated at his desk on the floor of the Senate. The injuries he sustains cause Sumner to be absent from the Senate for four years. The episode revealed the polarization in America, as Sumner became a martyr in the North and Brooks a hero in the South. Northerners were outraged. Southerners sent Brooks hundreds of new canes in endorsement of his assault. One was inscribed "Hit him again." Brooks claimed that he had not intended to kill Sumner, or else he would have used a different weapon. In a speech to the House defending his actions, Brooks stated that he "meant no disrespect to the Senate of the United States" or the House by his attack on Sumner. He was tried in a District of Columbia court, convicted for assault, and fined $300 ($8,000 in today's dollars), but received no prison sentence.

Farmer Hinton Rowan Helper publishes The Impending Crisis of the South, and How to Meet It, in which he argues that slavery in economically unwise, and particularly devastating to small farmers who do not own slaves. He writes that slavery is "the root of all the shame, poverty, ignorance, tyranny and imbecility" in the South. He also argues that slavery foolishly ties up economic resources in human beings when it might be spent on labor-saving improvements.

The African slave trade is prohibited in the Ottoman Empire

The Dred Scott Decision makes the Missouri Compromise unconstitutional and increases tension between North and South over slavery in the United States. Writing for the majority, Chief Justice Roger B. Taney asserted that blacks were "beings of an inferior order, and altogether unfit to associate with the white race, either in social or political relations, and so far inferior that they had no rights which the white man was bound to respect." This embarrassing decision represents a low point in the history of the United States Supreme Court.

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Harriet Wilson of Milford, New Hampshire, publishes Our Nig; or Sketches from the Life of a Free Black, the first novel by an African-American woman.

On October 16, John Brown leads 20 men, including five African-Americans, in an unsuccessful attempt to seize the Federal Armory at Harper's ferry, Virginia, with the goal of inspiring a slave insurrection. He was captured by US troops under the command of Colonel Robert E. Lee, tried, and hanged on December 2.