Slavery was the main cause of disunion. Slavery had been a controversial issue during the framing of the Constitution but had been left unsettled. The issue of slavery had confounded the nation since its inception, and increasingly separated the United States into a slaveholding South and a free North. The issue was exacerbated by the rapid territorial expansion of the country, which repeatedly brought to the fore the issue of whether new territory should be slaveholding or free. The issue had dominated politics for decades leading up to the war. Key attempts to solve the issue included the Missouri Compromise and the Compromise of 1850, but these only postponed an inevitable showdown over slavery.
The motivations of the average person were not inherently those of their faction; some Northern soldiers were even indifferent on the subject of slavery, but a general pattern can be established. Confederate soldiers fought the war primarily to protect a Southern society of which slavery was an integral part. From the anti-slavery perspective, the issue was primarily whether slavery was an anachronistic evil incompatible with republicanism. The strategy of the anti-slavery forces was containment—to stop the expansion of slavery and thereby put it on a path to ultimate extinction. The slaveholding interests in the South denounced this strategy as infringing upon their constitutional rights. Southern whites believed that the emancipation of slaves would destroy the South's economy, due to the large amount of capital invested in slaves and fears of integrating the ex-slave black population. In particular, many Southerners feared a repeat of the 1804 Haiti massacre (also known as "the horrors of Santo Domingo"), in which former slaves systematically murdered most of what was left of the country's white population—including men, women, children, and even many sympathetic to abolition—after the successful slave revolt in Haiti. Historian Thomas Fleming points to the historical phrase "a disease in the public mind" used by critics of this idea and proposes it contributed to the segregation in the Jim Crow era following emancipation. These fears were exacerbated by the 1859 attempt of John Brown to instigate an armed slave rebellion in the South.