I address this issue in my book, No Greater Calamity for the Country: North-South Conflict, Secession, and the Onset of Civil War. There was profound mistrust between North and South, which began to grow particularly severe after the Mexican War, which many northerners viewed as an effort by the south to conquer more territory amenable to slavery.
Over the 1850s, a few compromises were reached but each was harder to reach and left harder feelings. The 1850 compromise admitted California as a "free" state and left the other new territories "TBD." The only thing the south really got out of the deal was a strengthening of the Fugitive Slave Act. When northern states often refused to abide by their requirements, this increased the antagonism between the regions.
The fight over the status of Kansas territory was another major cause. the 1854 compromise agreed the status of Kansas would be settled by a vote of the residents. But everyone assumed Kansas would be a slave state, but when anti-slavery forces rushing into the state, a bloody civil war broke out. Eventually, Kansas was admitted as free territory, which further enraged southerners. Southerners recognized that if slavery couldn't expand into new territories, that eventually slave states would be more and more outnumbered in Congress and the institution would be doomed.
Other events that increased tensions included he Dred Scott decision, which said Congress was not allowed to regulate slavery in the territories and that black people, free or enslaved, could never be citizens; and John Brown's raid on the Harpers Ferry arsenal. Brown announced he intended to free slaves and instigate a revolt, which angered and frightened southerners. But the reaction in the north, where many people hailed Brown as a hero, angered the South even more.
These issues would probably have led to secession and war sometime. But the issue that triggered secession was the election of Lincoln. Lincoln promised he wouldn't end the institution of slavery but many southerners didn't believe him and everyone recognized his promise to prohibit expansion doomed slavery to an eventual end. Lincoln's election was enough to push seven deep south states (SC, GA, FL, AL, MS, LA, and TX) between December 1860 and February 1861.
The next event that led to the secession of four more states (VA, NC, Ark, TN) was the southern attack on Fort Sumter, a US fort in Charleston harbor that US forces refused to evacuate and Lincoln's subsequent call for 75,000 volunteers to suppress the rebellion. This pushed out the final four states.