John Middleton Clayton (July 24, 1796 - November 9, 1856) was an American statesman from Delaware who served as a U.S. Senator and as the U.S. Secretary of State from 1849 to 1850. He came from a Quaker family long prominent in the political life of Delaware. He graduated from Yale University in 1815, and in 1819 began to practice law in Dover, Delaware. For a time he was associated with his cousin, Thomas Clayton (1778-1854), who was also a prominent statesman and U.S. Senator.
Clayton became a member of the Delaware House of Representatives in 1824, and was the secretary of state from December 1826 to October 1828. In 1829 he was elected to the United State Senate. In 1831 he was a member of the Delaware Constitutional Convention, and resigned from the Senate in 1836. From 1837 to 1839 he was the Chief Justice of Delaware. In 1845 he again became a U.S. senator, where he opposed the annexation of Texas and the Mexican-American War, but advocated the active prosecution of the latter once it was begun. In March 1849 he became secretary of state in President Zachary Taylor's cabinet. His tenure at the Department of State was brief ending on the July 22, 1850, soon after Taylor's death. His notable accomplishment as Secretary of State was the negotiation of the Clayton-Bulwer Treaty with the British minister, Sir Henry Bulwer-Lytton. For the last time he became a U.S. Senator in March 1853 until his death in Dover, Delaware in 1856. His contemporaries considered Clayton one of the most skilled debaters and orators in the Senate.
In 1934, Delaware donated a statue of Clayton to the National Statuary Hall Collection.