While there were many war hawks who greatly favored going to war with Mexico, there were also many in the United States who vehemently opposed it. Most of the opposition came from the northern states. There were abolitionists who worried that newly captured territory could be used to expand slavery, which would greatly upset the finely tuned balance between free states and slaveholding states in the country. In an attempt to diffuse this standoff, Pennsylvania Democratic Congressman David Wilmot proposed a proviso which would prohibit slavery in any captured territory. When this proviso failed to pass the Senate, opposition to the war ramped up.

There was also political opposition to going to war. Many members of the Northern Whig and Liberty Parties felt that this war would greatly elevate the position and clout of President James Polk, a Democrat. On the other hand, most Democrats in Congress seemed to be in favor of the war.

Still, others opposed the war because they saw it as an unwarranted act of American aggression. Ohio Congressman Joshua Giddings summed it up well when he wrote, "In the murder of Mexicans upon their own soil, or in robbing them of their country, I can take no part either now or hereafter. The guilt of these crimes must rest on others."

In 1845, the Republic of Texas joined the United States through a Treaty of Annexation. The Republic of Texas had declared itself independent from Mexico in 1836, but lower-level hostilities between the two nations continued apace over the entire period of the Republic and included diplomatic disputes over Texas's boundaries as well as sporadic fighting. When Texas was annexed by the United States, these territorial disputes with Mexico were transferred as well. A diplomatic effort by the United States to purchase the disputed territory was rejected, and the continuing skirmishes were augmented by federal troops, so that the fighting was used as a basis for the United States to declare war on Mexico.

The annexation of Texas was hotly debated at the time, as a sizable portion of the United States population did not want another slave state. In addition to moral objections, the slaveholding Southern elite held a lot of political power, which Northern interests found objectionable. Although the Mexican War concluded in 1848, these North-South tensions would continue to erupt, finally culminating in the Civil War of 1861–1865.