Ephraim Mayo Clarke (21 August 1846 – 15 April 1921) was an Australian politician who was a member of the Legislative Council of Western Australia from 1901 until his death, representing South-West Province.

Clarke was born in Australind, in Western Australia's South West region.

Clarke entered parliament at a 1901 Legislative Council by-election, which had been caused by the death of the sitting member, William Spencer (a former mayor of Bunbury).

However, George Leake died in June 1902, and Clarke was not retained in the new ministry formed by Walter James.

After his initial election, Clarke was re-elected four more times (in 1902, 1908, 1914, and 1920), eventually joining the Nationalist Party.