Cavendish was the son of William Cavendish, 3rd Earl of Devonshire and his wife Lady Elizabeth Cecil. In 1661, he was elected Member of Parliament for Derbyshire in the Cavalier Parliament. He was a Whig under Charles II of England and James II of England and was leader of the anti-court and anti-Catholic party in the House of Commons, where he served as Lord Cavendish. He was re-elected MP for Derbyshire in the two elections of 1679 and in 1681. In 1684 he succeeded to the peerage as Earl of Devonshire on the death of his father and then sat in the House of Lords. He was a strong supporter of the "Glorious Revolution" of 1688 which brought William III of Orange to the throne, signing as one of the Immortal Seven the invitation to William.