| 1842 | John C. Frémont leads expedition along the Oregon Trail |
| 1848 | Gold discovered in California |
| 1850 | Compromise of 1850 |
| Fugitive Slave Act |
| 1852 | Harriet Beecher Stowe publishes Uncle Tom's Cabin |
| 1854 | U.S.-Japanese treaty allows for mutual trading |
| Republican Party founded |
| Kansas-Nebraska Act |
| 1854–1858 | Period of violence in Bleeding Kansas |
| 1857 | Dred Scott case |
| 1858 | Lincoln-Douglas debates |
| 1859 | John Brown's raid on Harpers Ferry |
| November 1860 | Abraham Lincoln elected president |
| December 1860 | South Carolina secedes from the Union |
| January 1861 | Mississippi, Florida, Alabama, Georgia, Louisiana, and Texas secede |
| February 1861 | Confederate States of America established |
| March 1861 | Lincoln inaugurated as president |