The main issue that triggered the Civil War in the U.S. was the question of slavery, particularly its expansion into newly acquired territories and states. The conflict arose from deep-rooted economic, social, and political differences between the North and the South. While the North was increasingly industrialized and favored abolition, the South relied heavily on an agrarian economy sustained by slave labor. Key events like the Missouri Compromise, the Kansas-Nebraska Act, and the Dred Scott decision intensified tensions. Ultimately, the election of Abraham Lincoln, viewed as a threat to slavery, led Southern states to secede, igniting the Civil War in 1861.