In many ways, Manifest Destiny and territorial expansion during this period did more to sow division in the United States than it did to unite it. There were Americans who felt that territorial expansion and conquest was, by its very nature, undemocratic. Many elites in the northeast worried that westward expansion would lead to the erosion of their power and influence as more states were added.

Much of the opposition to westward expansion centered around the issue of slavery. The US Constitution makes no provisions for the expansion of slavery into new territory. Naturally, pro-slave elements of the population wanted to spread slavery into new territories. At the same time, abolitionists and free-soilers opposed the spread of slavery.

This all led to contentious and sometimes violent clashes within American society. For instance, it took the United States nearly ten years to annex Texas, largely because of arguments over the spread of slavery into the region. In the 1840s, support and opposition to the war with Mexico fell largely along slavery and anti-slavery lines. Furthermore, if the Kansas–Nebraska Act, the fall of the Whig Party, and Bleeding Kansas are any indication, westward expansion nearly destroyed any semblance of unity within the United States. There are many historians who feel that Manifest Destiny was a leading cause of the Civil War itself.

This is not to say that westward expansion did nothing at all to unite the United States. The gold rush in California, for instance, brought together prospectors from all over the eastern part of the country to seek fortunes in a new territory. On a larger scale, the very idea that the continent was the God-given property of the United States was an idea that found acceptance by both pro-slavers and anti-slavers. It was the question of where slavery would be permitted that divided the country to a significant degree.