• Democrats vs. Republicans, 1850s-1890s
• Sectional dispute over slavery led to collapse of Second Party System by 1850s
• Whig Party collapsed, largely replaced in the North by the antislavery Republican Party after 1854
• Democrats became mainly a proslavery regional party based in the South
• Republican Abraham Lincoln's victory in 1860 election led to Civil War
• Republicans mostly dominated national politics in decades after Civil War

The Democratic Party was unable to maintain its alliance of southern and western farmers once slavery became the dominant political issue in America. The party therefore split into two factions: one representing proslavery Democrats in the South and another representing antislavery Democrats in the North. In 1860, the party ran two different candidates for the presidency, each representing a different part of the country. But the Whigs were unable to exploit this division. They, too, found themselves divided over slavery, with northern and southern Whigs increasingly struggling to establish common ground. Furthermore, following the deaths of Clay and Webster, the Whigs suffered from a lack of leadership. The beneficiary of this political void was the new Republican Party, founded in 1854. It ran its first candidate for president in 1856, John C. Fremont, and elected its first president, Abraham Lincoln, in 1860.

The Republicans were defined largely by their opposition to slavery, but it would be more accurate to say that they favored "free soil." That is, they were less opposed to slavery on humanitarian or moral grounds than they were anxious to preserve America's western lands for northern-style "free soil" farming—that is, farming in which the work was done by free white settlers rather than by black slaves. Before the Civil War, most Republicans were willing to tolerate slavery in the South, but they were vehemently opposed to the expansion of slavery farther into the West. Once in power, the Republicans did end slavery everywhere in America—but this was more an effect than a cause of the Civil War. Republicans also successfully pursued several measures that promoted western agrarian expansion. For example, the Republican Congress made public lands available to squatters through the Homestead Act, and built the Transcontinental Railroad linking western farmers with markets on the east coast.

After the Civil War, the Republicans dominated the presidency for more than twenty years, while the Democrats—a party strongly linked to the defeated Confederacy—exercised little influence outside the South.