The Kansas–Nebraska Act of 1854 (10 Stat. 277) was a territorial organic act that created the territories of Kansas and Nebraska. It was drafted by Democratic Senator Stephen A. Douglas, passed by the 33rd United States Congress, and signed into law by President Franklin Pierce. Douglas introduced the bill intending to open up new lands to develop and facilitate the construction of a transcontinental railroad. However, the Kansas–Nebraska Act effectively repealed the Missouri Compromise of 1820, stoking national tensions over slavery and contributing to a series of armed conflicts known as "Bleeding Kansas".

The United States had acquired vast amounts of land in the 1803 Louisiana Purchase, and since the 1840s, Douglas had sought to establish a territorial government in a portion of the Louisiana Purchase that was still unorganized. Douglas's efforts were stymied by Senator David Rice Atchison of Missouri and other Southern leaders who refused to allow the creation of territories that banned slavery; slavery would have been banned because the Missouri Compromise outlawed slavery in the territory north of latitude 36° 30′ north (except for Missouri). To win the support of Southerners like Atchison, Pierce and Douglas agreed to back the repeal of the Missouri Compromise, with the status of slavery instead decided based on "popular sovereignty". Under popular sovereignty, the citizens of each territory, rather than Congress, would determine whether slavery would be allowed.

Douglas's bill to repeal the Missouri Compromise and organize Kansas Territory and Nebraska Territory won approval by a wide margin in the Senate, but faced stronger opposition in the House of Representatives. Though Northern Whigs strongly opposed the bill, it passed the House with the support of almost all Southerners and some Northern Democrats. After the passage of the act, pro- and anti-slavery elements flooded into Kansas to establish a population that would vote for or against slavery, resulting in a series of armed conflicts known as "Bleeding Kansas". Douglas and Pierce hoped that popular sovereignty would help bring an end to the national debate over slavery, but the Kansas–Nebraska Act outraged Northerners. The division between pro-slavery and anti-slavery forces caused by the Act was the death knell for the ailing Whig Party, which broke apart after the Act. Its Northern remnants would give rise to the anti-slavery Republican Party. The Act, and the tensions over slavery it inflamed, were key events leading to the American Civil War.

In his 1853 inaugural address, President Franklin Pierce expressed hope that the Compromise of 1850 had settled the debate over the issue of slavery in the territories. For the Utah Territory and New Mexico Territory, lands acquired in the Mexican–American War, the Compromise left the issue of slavery to be decided by popular sovereignty. The Missouri Compromise, which banned slavery in territories north of the 36°30′ parallel, remained in place for the other U.S. territories acquired in the Louisiana Purchase, including a vast unorganized territory often referred to as "Nebraska". As settlers poured into the unorganized territory, and commercial and political interests called for a transcontinental railroad through the region, pressure mounted for the organization of the eastern parts of the unorganized territory. Though the organization of the territory was required to develop the region, an organization bill threatened to re-open the contentious debates over slavery in the territories that had taken place during and after the Mexican–American War.

The topic of a transcontinental railroad had been discussed since the 1840s. While there were debates over the specifics, especially the route to be taken, there was a public consensus that such a railroad should be built by private interests, and financed by public land grants. In 1845, Stephen A. Douglas, then serving in his first term in the U.S. House of Representatives, had submitted an unsuccessful plan to organize the Nebraska Territory formally, as the first step in building a railroad with its eastern terminus in Chicago. Railroad proposals were debated in all subsequent sessions of Congress with cities such as Chicago, St. Louis, Quincy, Memphis, and New Orleans competing to be the jumping-off point for the construction.

Several proposals in late 1852 and early 1853 had strong support, but they failed because of disputes over whether the railroad would follow a northern or a southern route. In early 1853, the House of Representatives passed a bill 107 to 49 to organize the Nebraska Territory in the land west of Iowa and Missouri. In March, the bill moved to the Senate Committee on Territories, which was headed by Douglas. Missouri Senator David Atchison announced that he would support the Nebraska proposal only if slavery were to be permitted. While the bill was silent on this issue, slavery would have been prohibited under the Missouri Compromise in the territory north of 36°30' latitude and west of the Mississippi River. Other Southern senators were as inflexible as Atchison. By a vote of 23 to 17, the Senate voted to table the motion, with every senator from the states south of Missouri voting to the table.

During the Senate adjournment, the issues of the railroad and the repeal of the Missouri Compromise became entangled in Missouri politics, as Atchison campaigned for re-election against the forces of Thomas Hart Benton. Atchison was maneuvered into choosing between antagonizing the state's railroad interests or its slaveholders. Finally, he took the position that he would rather see Nebraska "sink in hell" before he would allow it to be overrun by free soilers.

Representatives then generally found lodging in boarding houses when they were in the nation's capital to perform their legislative duties. Atchison shared lodgings in an F Street house shared by the leading Southerners in Congress. He was the Senate's President pro tempore. His housemates included Robert T. Hunter (from Virginia, chairman of the Finance Committee), James Mason (from Virginia, chairman of the Foreign Affairs Committee) and Andrew P. Butler (from South Carolina, chairman of the Judiciary Committee). When Congress reconvened on December 5, 1853, the group, termed the F Street Mess, along with Virginian William O. Goode, formed the nucleus that would insist on slaveholder equality in Nebraska. Douglas was aware of the group's opinions and power and knew that he needed to address its concerns. Douglas was also a fervent believer in popular sovereignty—the policy of letting the voters, almost exclusively white males, of a territory decide whether or not slavery should exist in it.