The main two topics that led to the American Civil War were:
Slavery
Slavery, especially the debate over expanding slavery into new western territories, was a major divide between the northern and southern states. The southern economy depended greatly on slave labor on plantations while the north opposed the expansion of slavery. This issue came to a head in the 1850s with the debate over the Kansas-Nebraska Act and whether new states entering the Union would be slave states or free states.
States' rights
The concept of states' rights, or that individual states should have more power than the federal government, was a longstanding belief in the southern states. The south argued that the federal government should not have the power to interfere in matters like slavery that they viewed as a state issue. In contrast, the northern view was that the federal government should have power over issues of national importance like slavery.
These two topics, slavery and states' rights, eventually led to the secession of southern states, the formation of the Confederacy, and the outbreak of the Civil War in 1861 as the south fought to preserve slavery and the north fought to preserve the Union. Other economic and political differences existed between north and south, but slavery and states' rights were the primary driving forces behind the momentous events that marked the Civil War era.
Hope this overview helps! Let me know if you have any other questions.