Ralph Waldo Emerson said "Mexico will poison us." He simply meant that the American acquisition of Mexican territory would be dangerous for the United States. Emerson was prescient enough to realize that the conflict would unleash hostility in the North and the South over the status of slavery. He was right, because Civil War did indeed erupt between the North and the South a mere thirteen years after the conclusion of the Mexican War (1846–1848).

Emerson, the leader of Transcendentalism, was not engaged in politics, so he was never directly involved in protesting the war. Henry David Thoreau, a friend and fellow disciple of Transcendentalism, spent a night in prison when he refused to pay a tax to support the Mexican War. Thoreau, unlike Emerson, actually wrote about his protest.

After Mexico had surrendered in 1848, it ceded vast lands to America. These territories increased the size of the United States by one third and ignited a firestorm. In 1848, a new political party, the Free Soil party, was founded: its goal was to keep slavery out of the West. One year later, the California Gold Rush brought thousands of settlers to California. The influx of so many people caused California to seek statehood. The South opposed this because admission of California as a free state would give the North a majority in the Senate. The Compromise of 1850 between the North and South merely delayed hostilities for a decade.

This comment, recorded in Emerson's journal in 1846, reflects a common feeling among antislavery Northerners. Emerson meant that the United States would win the war, but the acquisition of so much territory would "poison" the nation. His remark is usually taken to mean that the gaining of territory would reignite the political debates over the expansion of slavery, and since this very clearly did happen, Emerson was proven correct.

But there is a deeper level to Emerson's point than politics. He was an abolitionist, and like many of his time, he saw the Mexican War as the product of a "slave power" conspiracy in American politics. Waging an aggressive war against Mexico to gain territory was bad enough. But Emerson saw the war as an attempt to gain land precisely for the purpose of expanding slavery. In this sense, the Mexican War—or, more accurately ,the lands gained as a result of the war—were not just poisonous in the sense that they destabilized the politics of the time. For abolitionists, the war was fundamentally immoral on every level. Therefore it was a "poison" to the nation.

Politically and morally, the Mexican War would prove to be the final dose of slavery that had long poisoned the nation.

The concept of Manifest Destiny was a powerful force in the nineteenth century that motivated the United States to continually acquire new territory. It referred to the philosophy that God had destined the (white) United States to spread capitalism and democracy throughout North America. The phrase was first used in an issue of the Democratic Review in 1845, referring to the possible annexation of Texas. Before the Mexican-American War broke out, Ralph Waldo Emerson, a famous philosopher and writer, wrote,

The United States will conquer Mexico, but it will be as the man swallows the arsenic, which brings him down in turn. Mexico will poison us.

In this quote, Emerson was referring to the potential consequences of a war with Mexico. The problem was not only that many lives would be lost but also that the territory gained for the United States would reignite bitter debates about the issue of slavery.

Emerson's prediction proved to be prophetic. In the Treaty of Guadalupe Hidalgo, which marked the end of the Mexican-American War, the United States gained 525,000 square miles of new territory, which is now parts of Texas, Arizona, New Mexico, California, and several other states. The issue then arose of whether these states would be permit slavery or not. This exacerbated tensions that were already high, split apart political parties and the northern and southern states, and eventually led to the US Civil War. This was the deadliest conflict ever fought on American soil, during which hundreds of thousands of soldiers were killed and millions more injured. In this context, Emerson's quotation proved to be correct, as the acquisition of the Mexican territory poisoned American society and politics and helped to bring about the Civil War.