The primary argument for those opposing the Mexican-American war was that it would extend slavery in the southern colonies. Northern abolitionists vehemently opposed the war because the balance of power would be shifted more towards the slave-holding south. Polk used "manifest destiny" as the driver behind the annexation of Texas; however, most argued that the true reason was to advance slavery in the United States.

Politically, several prominent figures opposed the war. Most notably was Abraham Lincoln. Lincoln's point of contention was the border itself between Texas and Mexico. Lincoln was concerned that American troops were on Mexican soil when shots were fired. Most opponents of the war felt that the United States was the aggressor in this situation.

A final fear by the opponents was that the United States was using patriotism as an influence for the war. This was one of the first anti-war movements in the United States at the time. The acquisition of slave lands and the sketchy pretenses of the war itself founded the basis of the anti-war argument.