First Lord of the Treasury under whom the Isle of Man was bought from the Atholls.

The Revestment was his ministry's act, and the Commons said so afterwards without qualification. Speaking in 1791 on the Duke of Atholl's renewed claims, a member recalled the bargain made with the late Duke for his sovereignty over the Isle of Man in 1765, observed that Grenville was then the minister, and gave the reason of state behind it: that the sovereignty of the Island had been found incompatible with the interest of the public so long as it remained in the hands of an individual.

His earlier career ran through the Treasury and the Navy. He was made Treasurer of the Navy in a batch of civil appointments in March, and in 1763 he replaced Bute at the head of a triumvirate with Lord Halifax and Lord Egremont. He had been one of the Lords of the Treasury before that, and it was a letter of recommendation from Grenville that John Wilkes carried in his pocket to the electors of Berwick. Wilkes owed him more than that: it was through Grenville's influence that he had been made High Sheriff of Buckingham for 1754. The two men were on the opposite side of the privilege question within a decade, Grenville carrying the King's message to the House against Wilkes's motion.