The Anti-Nebraska Party was an American political party formed in response to the Kansas-Nebraska Act of 1854. Its founders, including Salmon P. Chase, held deep moral opposition to slavery, and were thus appalled by legislation that could lead to more slave-holding states. The Anti-Nebraska Party was created wholly to oppose slavery; it eventually morphed into the Republican Party.

This party was, in essence, an offshoot of the Know-Nothing party. Once the core reason for the Know Nothing party, anti-immigrant reform, had lost favor in the public eye its leader changed the message of the party. In almost every area in which the Know Nothings were powerful the Anti-Nebraska party carried in subsequent elections.