John B. Henderson (November 16, 1826 - April 12, 1913) was a United States Senator from Missouri. Born near Danville, Virginia, he moved with his parents to Lincoln County, Missouri, studied on his own while a farm hand, taught school, was admitted to the bar in 1844, and practiced. He 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 State militia in 1861, and was appointed and subsequently elected to the U.S. Senate as a Unionist to fill the vacancy caused by the expulsion of Trusten Polk; he was reelected in 1863 and served from January 17, 1862, to March 3, 1869. He was not a candidate for reelection. While in the Senate, Henderson was chairman of the Committee to Audit and Control the Contingent Expense (Thirty-ninth Congress) and a member of the Committee on Indian Affairs (Thirty-ninth and Fortieth Congresses). He was an unsuccessful candidate for Governor and Senator; in 1875 he was special United States attorney for prosecution of the Whiskey Ring at St. Louis. In 1877 he was appointed a commissioner to treat with hostile tribes of Indians.
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.