Disagreements over slavery between the North and the South had largely been deferred during the War of Independence and the formative decades of the U.S. However, during the first half of the nineteenth century, westward expansion and increasing economic development made these contradictions much more severe, leading to increasing levels of conflict that finally became too strong for the existing union to bear. One way to look at it is to think of the plantation and the factory as two rival modes of production, each of which grew tremendously during these decades, each of which was distinctively modern and American, and each of which had a voracious and ever-increasing appetite for land, labor, and resources—appetites that were in direct competition with one another as the economy developed and the nation expanded.
The first such conflict had to do with the land that the U.S. had acquired in the Louisiana Purchase in 1803. These lands were largely unsettled when the US had bought them under Jefferson. However, in 1818, the area that would become Missouri was almost populous enough to qualify the territory for statehood. This created tension because northerners worried that admitting a slave state would swing the balance of power in the US Senate and House of Representatives. The solution that was adopted was to admit another state, Maine, at the same time, as a Free State, and to adopt the 36° 30' parallel (the northern border of Missouri) as a future boundary between slave states and free states as the nation expanded westward. Under this compromise, which was formally adopted in 1819 when Missouri and Maine were admitted to the union, any territories within the Louisiana purchase admitted as new states below that parallel would be slave states and any territories north of that parallel would be admitted as free states.
If the Missouri Compromise addressed how these two different economic systems (the plantation and the factory) would divide up land, another event, the Nullification Crisis of 1832–33, addressed how each of them would be favored or disfavored in relation to foreign trade. The North was undergoing the industrial revolution and becoming a manufacturing center while, in the South, the plantation economy was expanding and increasingly relied upon foreign trade (particularly with the U.K.) to export agricultural products and import manufactured goods. The nullification crisis was set off by tariffs (taxes on imports), which the Constitution reserved for the Federal Government to impose (states, in other words, couldn't set their own trade policy even if their economic interests were very different). In particular, the Tariff of 1828, by raising the price on the importation of manufactured goods that could compete with northern factories, was seen to benefit the North and hurt the South, which needed those same cheap manufactured goods and, just as importantly, needed to export cotton and other agricultural goods in exchange.
Both of these needs (the North for protection from competition from foreign manufacturers and the South for access to foreign trade) were increasing as...
both the Northern factory economy and the Southern plantation economy gathered steam. In 1832, when Andrew Jackson, himself a southerner, refused, upon his election, to lower the Tariff, the state of South Carolina, led by Jackson's own vice president, John Calhoun, argued that it could simply "nullify" the tariff as a matter of state's rights. Since, Calhoun argued, the Federal Government was not a union of the people but a union of the states, and had been created by the states, any act of the union that the states didn't consent to had to be null and void. Jackson compromised; he vigorously denied the doctrine of nullification, but he also passed a new Tariff, the Tariff of 1832, which significantly addressed Southerners' concerns.
The next major event in this chain was the Mexican-American war, when, between 1846 and 1848, the U.S. invaded roughly half of Mexico and solidified its hold over Texas, which it had previously annexed. The Treaty of Guadalupe-Hidalgo ceded these vast swaths of territory to the U.S. and renewed the dispute, previously settled by the Missouri Compromise, over whether new territories admitted to the union would be slave or free. Unlike the Louisiana Purchase, the lands ceded by Mexico to the US in 1848 were not unsettled and, moreover, they were technically free territories, since Mexico had abolished slavery in 1829 (indeed, this was why U.S. settlers in Texas had revolted in the first place). The Wilmont Provisio, which would have forbade the expansion of slavery into any Mexican territory ceded to the U.S., failed in Congress.
The fight between North and South over whether the land, labor, and resources acquired during the Mexican-American war would be integrated into the plantation economy or the factory economy was on. This conflict would eventually become the Civil War. However, the war was held off for a decade by the Compromise of 1850, which divided the new territory roughly evenly into slave (Texas), free (California), and those allowed to decide for themselves (New Mexico and Utah), ended the slave trade in the District of Columbia and, as a bonus for the South, adopted the Fugitive Slave law, which required free states to hunt down and return to slavery anyone who escaped from the plantations.