William Middleton may refer to:

• William Middleton (by 1533–74 or later), MP for Carlisle
• Sir William Middleton, 3rd Baronet, British Member of Parliament for Northumberland, 1722–1757
• Sir William Middleton, 5th Baronet, British Member of Parliament for Northumberland, 1774–1795
• Sir William Fowle Middleton, 1st Baronet (1748–1829), British Member of Parliament for Ipswich and Hastings

• William Middleton (bishop) (died 1288), medieval bishop of Norwich
• William Middleton (pamphleteer) (died 1613), English churchman, academic and Protestant controversialist
• George "Bay" Middleton (William George Middleton, 1846–1892), equerry to John Spencer, 5th Earl Spencer
• William Shainline Middleton (1890–1975), American internist
• William James Middleton (1897–1918), World War I flying ace
• William D. Middleton (1928–2011), author, reporter and photographer
• William Middleton (American football) (born 1986), American football cornerback
• William Middleton (journalist, writer), journalist and writer
• Billy Middleton (1893–?), English football forward

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