The debate over the status of slavery in the territories failed to alleviate tensions between the slave-holding South and the free North, with the failure of the Compromise of 1850, a legislative package designed to address the issue. In his 1852 eulogy for Clay, Lincoln highlighted the latter's support for gradual emancipation and opposition to "both extremes" on the slavery issue. As the slavery debate in the Nebraska and Kansas territories became particularly acrimonious, Illinois Senator Stephen A. Douglas proposed popular sovereignty as a compromise; the measure would allow the electorate of each territory to decide the status of slavery. The legislation alarmed many Northerners, who sought to prevent the spread of slavery that could result, but Douglas's Kansas–Nebraska Act narrowly passed Congress in May 1854.

Lincoln did not comment on the act until months later in his "Peoria Speech" of October 1854. Lincoln then declared his opposition to slavery, which he repeated en route to the presidency. He said the Kansas Act had a "declared indifference, but as I must think, a covert real zeal for the spread of slavery. I cannot but hate it. I hate it because of the monstrous injustice of slavery itself. I hate it because it deprives our republican example of its just influence in the world...." Lincoln's attacks on the Kansas–Nebraska Act marked his return to political life.