Henderson was a member of the Missouri House of Representatives in 1848-1850 and 1856–1858, and was active in Democratic politics. He was commissioned a brigadier general in the Missouri State Militia in 1861, commanding federal forces in northeast Missouri. On January 17, 1862 Henderson was appointed to the U.S. Senate as a Unionist to fill the vacancy caused by the expulsion of Trusten Polk. Later that year, Henderson was elected to a full six-year term in the U.S. Senate.
13th Amendment
As a United States Senator representing a slave state, Henderson co-authored and co-sponsored the Thirteenth Amendment to the United States Constitution permanently prohibiting slavery in the United States. Henderson's original proposal, made January 11, 1864, was submitted to the Senate Judiciary Committee, and on February 10, 1864, it presented the Senate with a proposal combining the drafts of congressmen James Mitchell Ashley, James Falconer Wilson,, Charles Sumner, and Henderson. On January 31, 1865, the 13th Amendment was approved by the U.S. Congress, and on February 1, 1865, it was signed by President Abraham Lincoln. On April 14, 1865, Lincoln was assassinated before the amendment was ratified by the State of Georgia on December 6, 1865. While in the Senate, Henderson was chairman of the Committee to Audit and Control the Contingent Expense and a member of the Committee on Indian Affairs. During President Andrew Johnson's impeachment trial, Henderson broke party ranks, along with six other Republican senators and voted for acquittal. These seven Republican senators were disturbed by how the proceedings had been manipulated in order to give a one-sided presentation of the evidence. Senators William Pitt Fessenden, Joseph S. Fowler, James W. Grimes, John B. Henderson, Lyman Trumbull, Peter G. Van Winkle, and Edmund G. Ross of Kansas, who provided the decisive vote, defied their party and public opinion and voted against impeachment. After the trial, Ben Butler conducted hearings on the widespread reports that Republican senators had been bribed to vote for Johnson's acquittal. In Butler's hearings, and in subsequent inquiries, there was increasing evidence that some acquittal votes were acquired by promises of patronage jobs and cash cards. Henderson was not a candidate for reelection to the Senate in 1868 and left the U.S. Senate on March 4, 1869. Henderson was an unsuccessful candidate for Governor of Missouri and later U.S. Senator. In 1875, he was appointed by Ulysses Grant as a special United States attorney for prosecution of the Whiskey Ring at St. Louis. After attempting to stifle Henderson's investigation of the president's personal secretary, Grant fired Henderson on the basis that Henderson's statements to a grand jury regarding Grant were impertinent. Following criticism, Grant appointed a new special prosecutor, James Broadhead, to continue the investigation. In 1877, Henderson was appointed a commissioner to treat with hostile tribes of Indians.
Later life
Henderson moved to Washington, D.C. in 1888, was a writer, and resided in the capital until his death in 1913. Interment was in Green-Wood Cemetery, Brooklyn, New York.
