After the expiration of his term as attorney general, he was again elected to the U.S. Senate, where he urged compromise on the issue of slavery to prevent the breakup of the United States.

In December 1860, he authored the Crittenden Compromise, a series of resolutions and constitutional amendments he hoped would avert the Civil War, but Congress would not approve them.

When the U.S. Senate term of Martin D. Hardin, one of Slaughter's unpopular nominees, expired in 1817, the Kentucky General Assembly chose Crittenden to fill the vacancy.

[27] He found state politics more interesting, however, and this fact, coupled with increased financial responsibilities incurred by the birth of his third and fourth children, prompted his decision to resign his seat on March 3, 1819.

When Crittenden consented to run, New Court supporters nominated the state's Attorney General Solomon P. Sharp and Lewis Sanders, a prominent lawyer.

[14] In 1828, Adams nominated him to replace Kentuckian Robert Trimble as an associate justice of the Supreme Court, but Jackson supporters in the Senate refused to confirm him.

[54] Early in his term, Crittenden vociferously opposed Senator Thomas H. Benton's proposal to spend the federal budget surplus on public land graduation and military fortifications along the eastern seaboard.

In 1836, he resisted petitions by the Quakers to abolish slavery in Washington, D.C., but he also opposed radical pro-slavery measures such as John C. Calhoun's proposal to ban abolitionist literature from being delivered by mail in the Southern states.

[62] During the balloting at the party's 1839 convention, candidates Clay and General Winfield Scott played cards with Crittenden and Whig politician George Evans at the Astor House hotel in New York City.

[65] Only a week after being appointed by Harrison, Crittenden was dispatched to New York City to mediate tensions with Great Britain over the sinking of the steamboat Caroline by a group of Canadian militia, who were attempting to suppress a rebellion in Canada.

[73] Clay tried to moderate his views on annexation, but his changes of position drew opposition from supporters of both sides of the issue as he attempted to find a middle ground.

[76] Lewis Cass, a senator from Michigan, supported an immediate termination of the joint occupation agreement and maintained that a war with the British over the matter was inevitable.

[76] Crittenden disagreed, and insisted that Britain be given two years notice before the joint occupation of the territory was ended in order to allow time for a diplomatic resolution.

[79] A few Whigs joined the Democratic majority in Congress to ratify the treaty and defeat the Wilmot Proviso, which would have banned slavery in the newly acquired territory.

[85] He would also have to abandon his growing legal practice before the Supreme Court and would lose input on national issues of importance to him such as the territorial questions that grew out of the Mexican War.

[93] Appeals came in from both Whig and Democratic leaders across the country urging him to serve in the cabinet; Taylor was inexperienced, and many felt that without Crittenden to guide him, his administration would fail.

[95] Crittenden's input is believed to have contributed significantly to the appointments of John M. Clayton as Secretary of State and Orlando Brown as Commissioner of Indian Affairs.

"[24] In response to Crittenden's call for financial support for the improvement of public education, the General Assembly passed a common school law on February 26, 1849.

[99] The Assembly also reserved tolls collected on the Kentucky, Green, and Barren rivers for education, and passed a two percent property tax to fund the state's schools.

[100] With the question of slavery becoming even more critical following the territorial acquisitions of the Mexican–American War, John C. Calhoun delivered an inflammatory address in December 1848 urging leaders of the southern states to resist "Northern aggression", even if it meant secession from the Union.

Specifically, some of the claimants objected to a legal provision, passed by Congress years after the Adams–Onís Treaty, that allowed the secretary of the treasury to refuse to pay claims awarded by Florida courts that he found not to be "just and equitable".

Crittenden, whose term as attorney general also expired in 1853, had publicly announced that he wished to return to the Senate after his service in President Fillmore's cabinet, and upon learning this, Underwood and Morehead both withdrew from the race.

During the week-long trial, which began in April 1854, Crittenden emphasized inconsistencies in the accounts of eyewitnesses and called prominent character witnesses such as Louisville mayor James Stephens Speed, Congressman William Preston, and Courier-Journal editor George D. Prentice.

Because the prosecution sought the death penalty, Crittenden asserted that if the jury rendered an erroneous conviction, they would have no peace of mind knowing they had sentenced an innocent man to hang.

Though it was believed that Republicans in general, including their representatives on the committee, were disposed to accept Crittenden's compromise or one substantially similar to it, President-elect Lincoln had already instructed his trusted allies in the legislature to resist any plan to extend slavery into the territories.

After the rejection of Crittenden's plan in committee, Florida, Mississippi, Alabama, and Georgia followed South Carolina's lead and passed ordinances of secession.

With the senators from southern states (both those that had seceded and those that had not) refusing to vote, Republicans were left with a majority in the chamber and passed Clark's substitute resolution, effectively killing Crittenden's proposal.

Having learned that John Archibald Campbell, an Alabamian serving on the Supreme Court, had decided to resign in light of his state's secession, President Lincoln proposed to appoint Crittenden to the vacant seat.

George's brother, Thomas Leonidas Crittenden, had been a member of Buckner's State Guard, but joined the Union Army in September 1861 and was advanced to the rank of brigadier general, serving under Don Carlos Buell.

[141] Shortly after his nomination, Crittenden and his wife were en route to an alum spring in Indiana to seek treatment to alleviate the symptoms of his failing health when he collapsed in Louisville.