Illinois Democrats redrew the boundaries of his district to favor their candidate, and Yates narrowly lost his bid for a third term in Congress.

"[15] Governor Yates continued to be an outspoken opponent of slavery, and at the opening of the Civil War was very active in raising volunteers.

[6] He convened the legislature in extra session on April 12, 1861, the day after the attack on Fort Sumter, and took military possession of Cairo, garrisoning it with regular troops.

[18] After the Battle of Shiloh, Yates personally took hospital supplies to the succor of the wounded from his state, as did the wartime governors of Wisconsin (Salomon) and Indiana (Morton).

[19] In September 1862, Yates attended the Loyal War Governors' Conference in Altoona, Pennsylvania, which ultimately gave Abraham Lincoln support for his Emancipation Proclamation.

[2][3] During the Civil War, Yates benefited from his relations with Lincoln to bring significant federal financial resources to the State of Illinois and Chicago in particular.

[citation needed] Chicago became the location for the largest prisoner of war encampment, Camp Douglas, which had been erected on the former estate of Lincoln's political opponent, the late Senator Stephen A. Douglas (similarly, the estate of Confederate General Robert E. Lee in Arlington, Virginia was taken over by the government for use as a military cemetery).

Yates, fearing that the Democrats had been infiltrated by the pro-secession Knights of the Golden Circle,[22] dissolved the Illinois legislature on June 10, 1863, declaring that "the past history of the Assembly hold[s] out no reasonable hope of beneficial results to the citizens of the State, or the army in the field, from its further continuance".

[24] During the impeachment proceedings against Andrew Johnson, Yates spoke in favor of convicting the President, whom he described as a "most pestilent disturber of public peace ... who, through murder succeeded to the chief command and seeks to betray us to the enemy.

After leaving the Senate, he was appointed by President Grant as a United States commissioner to inspect a land subsidy railroad.