
Before Taylor's death, Kentucky Senator Henry Clay had devised a compromise bill which included provisions that had some appeal to both sides of the issue. A few days before President Taylor's death, Fillmore told Taylor 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, even though this went against his president's wishes.
Fillmore became President on July 9, 1850. When Fillmore took office, the entire cabinet offered their resignations. Fillmore accepted them all and appointed men who, favored the Compromise of 1850 (except for Treasury Secretary Thomas Corwin). Fillmore offered the post of Attorney General to Crittenden, whose term as Governor of Kentucky was coming to an end. Crittenden felt that the rift in the Whig Party was improving, so he accepted the offer and resigned the governorship. Fillmore requested an opinion from his new Attorney general on the constitutionality of the Fugitive Slave law, one of the bills involved in the Compromise of 1850. This Act required northerners to return runaway slaves and made it an offence to harbor them. Specifically, Fillmore asked if the law suspended the writ of habeas corpus (a legal action or writ by means of which detainees can seek relief from unlawful imprisonment.) Crittenden said that it did not not. Some historians believe that Crittenden's opinion was probably motivated by a desire to see the Compromise pass. By giving this opinion, northerners were more willing to go along with the compromise. The opinion convinced Fillmore to sign the bill, keeping the compromise afloat.
While serving as Fillmore's Attorney General, Crittenden also acted as Secretary of State during the illness of Daniel Webster. During this time, he wrote a vigorous warning to both Britain and France about interfering in the question of Cuban independence. He also supported the United States' traditional policy of non-interference in Europe during the celebrated visit of Hungarian revolutionary Louis Kossuth to the United States in 1851.

Crittenden's term as attorney general expired in 1853 and he announced that he wished to return to the Senate after his service in President Fillmore's cabinet. By this time a rift had developed between Crittenden and Henry Clay and the latter refused to cooperate in proposals to support Crittenden's return to the senate despite Clay's failing health. Three weeks before Clay's death in 1852, he sent for Crittenden, and the two were reconciled. Critteden delivered a eulogy for Clay in September 1852, publicly dispelling the feud.
After Clay's death, Crittenden became the most prominent Whig leader in Kentucky. He encouraged the party to support the nomination of Millard Fillmore for the presidency in 1852, but the nomination ultimately went to Winfield Scott. Crittenden was proposed as the nominee for vice-president, but he declined. Democrat Franklin Pierce carried the state by 2,700 votes in the general election of 1852 and Democrats also captured the governorship that year. Both were strong indicators of the demise of the Whig Party.
Crittenden died in 1863. Two years earlier he had lobbied President Abraham Lincoln to agree to tolerate Kentucky's neutrality in the civil war.