The key issue that ignited the American Civil War was slavery, particularly its expansion into newly acquired territories and states. Tensions escalated due to events like the Missouri Compromise and the Compromise of 1850, which attempted to maintain a balance between slave and free states. The publication of Harriet Beecher Stowe's "Uncle Tom's Cabin" galvanized public opinion against the institution of slavery. The 1857 Dred Scott decision by the Supreme Court further inflamed the situation by denying citizenship and rights to African Americans. Ultimately, the election of Abraham Lincoln, perceived as a threat to slavery, led Southern states to secede, triggering the War.