The Civil War didn't start until 1861, but it's clear that it was always likely from the very beginning of the American experiment. The issue of slavery so divided the Founders that they came up with a whole lot of compromises and workarounds to not have to deal with it, kicking that particular can down the road.
However, this meant that the industrialized North and the slave-owning South saw their economic fortunes begin to diverge. The world economy was changing around them, and the South began to see its cotton plantation profit margins shifting, making slavery ever more crucial to staying wealthy. Meanwhile, new states became part of the Union, and any compromise previously reached became increasingly untenable.
The result was that 11 states seceded from the Union, naming themselves the Confederated States of America and publishing Articles of Secession in which they mention no fewer than 84 times that they would not give up their "peculiar institution" that was so key to their way of life.
While Jefferson Davis, Confederate president, repeatedly insisted that it was about no one else getting to make the rules about slavery, for President Lincoln, it was as much about preserving the Union as anything. Two great armies marched, and memorable generals like Robert E. Lee and Ulysses S. Grant led them. Four years later, with the South in ruins, slavery was ended, the president was dead and more than 5% of the population with him. Time to see if you recall how exactly it all went down!