He was born in Edwinstowe, Nottinghamshire, the son of the 3rd Earl of Clare and his wife Grace Pierrepont. Grace was daughter of The Honorary William Pierrepont and granddaughter of the 1st Earl of Kingston-upon-Hull.
Holles was elected Member of Parliament for Nottinghamshire as Lord Houghton on 14 January 1689, but was called to the House of Lords two days later when his father died and he became the 4th Earl of Clare.
He was created the 1st Duke of Newcastle-upon-Tyne, of the 2nd creation, in 1694. The Duke of Newcastle-upon-Tyne is a title which was created three times in British history. The first creation had become extinct when Henry Cavendish, 2nd Duke of Newcastle-upon-Tyne died with out a male heir.
The Honorary John Holles (1662–1666) Lord Haughton (1666–1689) Lord Haughton, Member of Parliament (1689–1689) The Rt. Honorary The Earl of Clare (1689–1694) His Grace The Duke of Newcastle-upon-Tyne (1694–1698) His Grace The Duke of Newcastle-upon-Tyne, Knight of the Order of the Garter (1698–1705) His Grace The Duke of Newcastle-upon-Tyne, Knight of the Order of the Garter, Personal Computer (1705–1711).
