The son of Prime Minister George Grenville, Grenville entered the Commons in 1782 and soon became a close ally of Prime Minister William Pitt the Younger, serving in the government as Paymaster of the Forces from 1784 to 1789. In 1789, Grenville entered the Cabinet as Home Secretary, and became Leader of the House of Lords when he was raised to the peerage the next year as Baron Grenville of Wotton-under-Bernewood. The next year, in 1791, he succeeded the Duke of Leeds as Secretary of State for Foreign Affairs. Grenville's decade as Foreign Secretary was a dramatic one, seeing the Wars of the French Revolution. During the war, Grenville was the leader of the party that focused on the fighting on the continent as the key to victory, opposing the faction of Henry Dundas which favored war at sea and in the colonies. Grenville left office with Pitt in 1801 over the issue of Catholic Emancipation.
In his years out of office, Grenville became close to the opposition Whigs leader Charles James Fox, and when Pitt returned to office in 1804, Grenville did not take part. Following Pitt's death in 1806, Grenville became the head of the "Ministry of all The Talents", a coalition between Grenville's supporters, the Foxite Whigs, and the supporters of former Prime Minister Lord Sidmouth, with Grenville as First Lord of the Treasury and Fox as Foreign Secretary as joint leaders. Grenville's younger brother, Thomas Grenville, served briefly as First Lord of the Admiralty. The Ministry ultimately accomplished little, failing either to make peace with France or to accomplish Catholic emancipation (the later attempt resulting in the ministry's dismissal in March, 1807. It did have one significant achievement, however, in the abolition of the slave trade in 1807.
In the years after the fall of the ministry, Grenville continued in opposition, maintaining his alliance with Lord Grey and the Whigs, criticizing the Peninsular War and, with Grey, refusing to join Lord Liverpool's government in 1812. In the post-war years, Grenville gradually moved back closer to the Tories, but never again returned to the cabinet. His political career was ended by a stroke in 1823. Grenville also served as Chancellor of Oxford University from 1810 until his death in 1834.
The Ministry of All the Talents, February 1806 - March 1807