William was born in Nottinghamshire in 1592, and was the son of Sir Charles Cavendish.

In 1628, aged 36, he was made Earl of Newcastle and Baron Cavendish of Bolsover.

He was elevated to Marquess of Newcastle in 1643.

William exiled himself from England in 1644, after the Royalist defeat at Marston Moor. He lived in Hamburg, Paris, Rotterdam and later Antwerp, before returning to England in 1650 when he was appointed a member of Charles II's privy council.

In 1665 he was created 1st Duke of Newcastle.

William died at Welbeck in Nottinghamshire in December 1676. His son, Henry, became 2nd Duke of Newcastle.

William was a scholar, a poet, a gentleman and a brilliant horseman. He was also immensely wealthy. In 1633, he allegedly spent 20,000 pounds on entertainment when King Charles I visited his estate at Welbeck. He also was said to have loaned the King 10,000 pounds in 1638.