Arguments against Manifest Destiny: God would not grant any country the right to expand at the expense of the native inhabitants whose land would be taken, and the lives of those who would die in wars over territory. The term "Manifest Destiny" is merely an excuse for the U.S. to take other people's lands. Furthermore, spreading too far across the country will weaken the country's vital institutions, making the Union vulnerable.

Opponents of Manifest Destiny, on the other hand, argued that a just God would not grant a right to American expansion at the price of the rights and lives of tens of thousands of innocent native people. They protested that the idea of "Manifest Destiny" was extremely dangerous since it gave the U.S. an excuse to commit barbarous acts at will. When expansion led to war, opponents became even more vocal.