William Middleton may refer to:
Politicians
- 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
Others
- 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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