Born in Cambridge, England, he was the eldest son of Charles Yorke, Lord Chancellor, by his first wife, Catherine Freman.

Hardwicke was Member of Parliament for Cambridgeshire from 1780 to 1790, following the Whig traditions of his family, but after his succession to the earldom in 1790 he supported William Pitt The Younger, and took office in 1801 as Lord Lieutenant of Ireland (1801–1806), where he supported Catholic emancipation.

He was sworn of the Privy Council in 1801, created a Knight of the Garter in 1803, and was a fellow of the Royal Society.

Lord Hardwicke married Lady Elizabeth, daughter of James Lindsay, 5th Earl of Balcarres, in 1782.

Lord Hardwicke died on 18 November 1834, aged 77, and was buried St Andrew's Church in Wimpole, Cambridgeshire, in a tomb by Richard Westmacott the Younger.