Slavery is one of the causes of American Civil War. Support for secession was strongly correlated to the number of plantations in the region. States of the Deep South, which had the greatest concentration of plantations, were the first to secede. The upper South slave states of Virginia, North Carolina, Arkansas, and Tennessee had fewer plantations and rejected secession until the Fort Sumter crisis forced them to choose sides. Border states had fewer plantations still and never seceded.

As of 1860 the percentage of Southern families that owned slaves has been estimated to be 43 percent in the lower South, 36 percent in the upper South and 22 percent in the border states that fought mostly for the Union. Half the owners had one to four slaves. A total of 8000 planters owned 50 or more slaves in 1850 and only 1800 planters owned 100 or more; of the latter, 85% lived in the lower South, as opposed to one percent in the border states.

Ninety-five percent of African-Americans lived in the South, comprising one third of the population there as opposed to one percent of the population of the North, chiefly in larger cities like New York and Philadelphia. Consequently, fears of eventual emancipation were much greater in the South than in the North.

The Supreme Court decision of 1857 in Dred Scott v. Sandford escalated the controversy. Chief Justice Roger B. Taney's decision said that slaves were "so far inferior that they had no rights which the white man was bound to respect". Taney then overturned the Missouri Compromise, which banned slavery in territory north of the 36°30' parallel. He stated, "The Act of Congress which prohibited a citizen from holding and owning enslaved persons in the territory of the United States north of the line therein is not warranted by the Constitution and is therefore void." Democrats praised the Dred Scott decision, but Republicans branded it a "willful perversion" of the Constitution. They argued that if Scott could not legally file suit, the Supreme Court had no right to consider the Missouri Compromise's constitutionality. Lincoln warned that "the next Dred Scott decision" could threaten Northern states with slavery.

Lincoln said, "This question of Slavery was more important than any other; indeed, so much more important has it become that no other national question can even get a hearing just at present." The slavery issue was related to sectional competition for control of the territories,[32] and the Southern demand for a slave code for the territories was the issue used by Southern politicians to split the Democratic Party in two, which all but guaranteed the election of Lincoln and secession. When secession was an issue, South Carolina planter and state Senator John Townsend said that, "our enemies are about to take possession of the Government, that they intend to rule us according to the caprices of their fanatical theories, and according to the declared purposes of abolishing slavery." Similar opinions were expressed throughout the South in editorials, political speeches and declarations of reasons for secession. Even though Lincoln had no plans to outlaw slavery where it existed, whites throughout the South expressed fears for the future of slavery.

Southern concerns included not only economic loss but also fears of racial equality. The Texas Declaration of Causes for Secession said that the non-slave-holding states were "proclaiming the debasing doctrine of equality of all men, irrespective of race or color", and that the African race "were rightfully held and regarded as an inferior and dependent race". Alabama secessionist E. S. Dargan warned that whites and free blacks could not live together; if slaves were emancipated and remained in the South, "we ourselves would become the executioners of our own slaves. To this extent would the policy of our Northern enemies drive us; and thus would we not only be reduced to poverty, but what is still worse, we should be driven to crime, to the commission of sin."

Beginning in the 1830s, the US Postmaster General refused to allow mail which carried abolition pamphlets to the South. Northern teachers suspected of any tinge of abolitionism were expelled from the South, and abolitionist literature was banned. Southerners rejected the denials of Republicans that they were abolitionists. The North felt threatened as well, for as Eric Foner concludes, "Northerners came to view slavery as the very antithesis of the good society, as well as a threat to their own fundamental values and interests."

During the 1850s, slaves left the border states through sale, manumission and escape, and border states also had more free African-Americans and European immigrants than the lower South, which increased Southern fears that slavery was threatened with rapid extinction in this area. Such fears greatly increased Southern efforts to make Kansas a slave state. By 1860, the number of white border state families owning slaves plunged to only 16 percent of the total. Slaves sold to lower South states were owned by a smaller number of wealthy slave owners as the price of slaves increased.

Even though Lincoln agreed to the Corwin Amendment, which would have protected slavery in existing states, secessionists claimed that such guarantees were meaningless. Besides the loss of Kansas to free soil Northerners, secessionists feared that the loss of slaves in the border states would lead to emancipation, and that upper South slave states might be the next dominoes to fall. They feared that Republicans would use patronage to incite slaves and antislavery Southern whites such as Hinton Rowan Helper. Then slavery in the lower South, like a "scorpion encircled by fire, would sting itself to death."