Three Big Things:
1. Slavery. While not the only factor, it was by far the largest. Without it, there would have been no war. Seceding southern states issued their own “declarations” explaining the causes which impelled them to the separation. The issue? Slavery, threats to slavery, insufficient protection of slavery, criticisms of slavery. Oh, and slavery.
2. The Election of 1860. Abraham Lincoln’s victory signaled to the South that the system – democracy, compromise, voting – no longer worked. Their voice, it seemed, was no longer even a factor in how the nation was run. Lincoln's election was the final straw, since he was perceived as a threat to… what else? Slavery.
3. Overconfidence. Few on either side anticipated the possibility of an extended war, or the kinds of death and violence which were to come. Had those making decisions had any hint of what would unfold, one wonders if they’d have pursued other solutions a bit more vigorously.