After Lincoln won, many Southern leaders felt that disunion was their only option, fearing that the loss of representation would hamper their ability to enact pro-slavery laws and policies. In his second inaugural address, Lincoln said that "slaves constituted a peculiar and powerful interest. All knew that this interest was, somehow, the cause of the war. An initial seven southern slave states responded to Lincoln's victory by seceding from the United States and, in February 1861, forming the Confederacy. The Confederacy seized U.S. forts and other federal assets within their borders. Led by Confederate President Jefferson Davis, the Confederacy asserted control over about a third of the U.S. population in eleven of the 34 U.S. states that then existed. Four years of intense combat, mostly in the South, ensued.

The American Civil War was fought between the Union("the North") and the Confederacy ("the South"), the latter formed by states that had seceded. The central cause of the war was the dispute over whether slavery would be permitted to expand into the western territories, leading to more slave states, or be prevented from doing so, which was widely believed would place slavery on a course of ultimate extinction.