William Clayton can refer to:
- William Clayton (Liverpool MP) (died 1715), Member of Parliament for Liverpool 1698–1708
- Sir William Clayton, 1st Baronet (died 1744), Member of Parliament for Bletchingley 1715–1744
- William Clayton, 1st Baron Sundon (1671–1752), MP for Woodstock, St Albans, Westminster, Plympton Erle and St Mawes
- William Clayton (c. 1718–1783), Member of Parliament for Bletchingley 1745–1761 and Great Marlow 1761–1783
- Sir William Clayton, 4th Baronet (1762–1834), Member of Parliament for Great Marlow 1783–1790
- Sir William Robert Clayton, 5th Baronet (1786–1866), Member of Parliament for Great Marlow 1832–1842
- William Clayton (Mormon), Mormon pioneer
- Sir William Clayton (architect), prominent New Zealand architect
- William L. Clayton, US assistant secretary of state for economic affairs (see the Bretton Woods system)
- William Clayton, publisher of Astounding Stories
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