
The Taylor-Fillmore ticket won the election, and with it inherited the tensions that existed between free states and slave states. Two years into Taylor's term, Congress was debating what was known as the "Crisis of 1850" in which pro-slavery Southerners were demanding that all the new territories should be open to slavery and anti-slavery Northerners demanded that these territories be free from slavery. The most recently admitted state, Texas, claimed a large part of New Mexico, and also wanted the U.S. to assume its debt. California settlers were petitioning for immediate admission as a free state, bypassing the territorial stage. There was also a disputes about the apprehension of slaves who escaped to the free states.
It was expected that as a southerner, Taylor would side with the slave states. But he surprised his fellow Southerners by urging the immediate admission of California and New Mexico as free states. Ironically, it was Fillmore, the Northerner, who supported slavery in all or most of the new territory to prevent a break with the South. He wrote: "God knows that I detest slavery, but it is an existing evil and we must endure it and give it such protection as is guaranteed by the Constitution."
Senator Henry Clay proposed a compromise bill which included provisions desired by both sides. Fillmore told his President that if the vote on Clay's bill was tied, he as President of the Senate would cast his tie-breaking vote in favor.
Zachary Taylor died suddenly on July 9, 1850, and Fillmore became President. Taylor had been expected to veto the Compromise bill. When Fillmore took office, Taylor's entire cabinet offered their resignations, most of which Fillmore accepted. He replaced all of them except for Treasury Secretary Thomas Corwin. Those whose resignations he accepted were replaced men who supported the Compromise of 1850.
The debate over the compromise bill was hotly contested. The bill put before both Houses of Congress was less favorable to southerners than the one originally debated and Fillmore urged Congress to pass the original bill. This added to the intensity of the debate. Henry Clay, the great compromiser, was in poor health at the time. An exhausted Clay left Washington to recuperate, leaving the job of getting the bill passed on the shoulders of Senator Stephen A. Douglas of Illinois.
On August 6, 1850, Fillmore sent a message to Congress recommending that Texas's debts be paid provided Texas abandoned its claims in New Mexico. This helped to move a number of northern Whigs in Congress away from their insistence upon a stipulation that all the Mexican lands must be closed to slavery. Douglas modified the compromise with this change in mind. He split the compromise bill into five separate Senate bills. These bills called for:
1. Admission of California as a free state
2. Settlement of the Texas boundary and US accepting responsibility for Texas' debts
3. Creation of New Mexico Territory, which would be open to slavery
4. Passage of the Fugitive Slave Act
5. Abolition of the slave trade (but not slavery), in the District of Columbia.

Each of these were passed in both houses. But the Compromise disrupted the Whig party, which did badly in the fall 1850 mid-term elections in the north. Fillmore would he the last President that the Whig Party ever had.
Of the measures, probably the most controversial was the Fugitive Slave Act. Not only did it authorize the capture of slaves in free states, it also made it an offence for law enforcement officers not to arrest an alleged runaway slave. They could be fined up to $1,000 (about $28,000 in 2015 dollars). Law enforcement officials everywhere were required to arrest people suspected of being a runaway slave on as little as a claimant's sworn testimony of ownership. The suspected slave was not entitled to a jury trial and could not testify on his or her own behalf. Any person aiding a runaway slave by providing food or shelter was subject to six months' imprisonment and a $1,000 fine. Slave owners could provide an affidavit to a Federal marshal to capture an escaped slave and that was deemed sufficient authority. Since any suspected slave was not eligible for a trial, the law often resulted in the kidnapping and conscription of free African-Americans into slavery. Suspected fugitive slaves could not defend themselves against accusations.
In 1854, the Wisconsin Supreme Court became the first (and only) state court to declare the Fugitive Slave Act unconstitutional, but this ruling was overturned in the United States Supreme Court in the case of Ableman v. Booth in 1859. Vermont attempted to circumvent the law by passing the "Habeas Corpus Law" in November of 1850. This law required Vermont judicial and law enforcement officials to assist captured fugitive slaves. In response, President Fillmore threatened to use the army to enforce the Fugitive Slave Act in Vermont. No test case took place.
The Fugitive Slave Law brought the issue of slavery to the forefront in the North. Harriet Beecher Stowe wrote Uncle Tom's Cabin (1852) to highlight the evils of slavery. Many abolitionists defied the law openly, such as Reverend Luther Lee, pastor of the Wesleyan Methodist Church of Syracuse, New York. Some abolitionist groups would attempt the rescue and release of slaves passing through their area. African-American leader Harriet Tubman was active in the "underground railroad" which helped to transport escaped slaves to Canada, which became a major destination for escaped slaves. The African-descended population of Canada increased from 40,000 to 60,000 between 1850 and 1860.

When the Civil War broke out, the law essentially ceased to be enforced. Abolitionist Generals such as Benjamin Butler refused to return runaway slaves. Butler would confiscate slaves as contraband of war and set them free, believing that the loss of workers would damage the Confederacy. Congress eventually passed legislation that forbade US forces to return escape slaves.
Fillmore became very unpopular with northern Whigs for signing and enforcing the Fugitive Slave Act. Fillmore sought his party's nomination in the election of 1852, but when the Whigs held their National Convention in June that year, he was unsuccessful. He led narrowly on the early ballots, but was short of a majority and could gain no votes. On the 52nd ballot, Daniel Webster's delegates switched to General Winfield Scott, winning him the nomination on the 53rd ballot.