William Grenville was born on 24 October 1759, the third son and sixth of nine children born to George Grenville and Elizabeth Wyndham. In 1792, he married Anne Pitt. She was the daughter of Thomas Pitt, first Baron Camelford. The Grenville and Pitt families were intertwined, since Pitt the Elder (the Earl of Chatham) had married Hester Grenville, sister of George Grenville. Consequently, Lord Grenville and Pitt the Younger were cousins.
Lord Grenville was educated at Eton and Christ Church College Oxford. He graduated in 1780 having won the Chancellor's prize for Latin verse in 1779. Grenville was academically very gifted and had a keen interest in and extensive knowledge of classical literature. He spent a lot of time editing the correspondence of his uncle, Lord Chatham. He trained for the Bar but was never called since he entered parliament in 1782 as MP for the family's borough of Buckingham. He continued to represent the constituency until he was elevated to the peerage in 1790.
Grenville held continual ministerial office during his parliamentary career. He was Chief Secretary for Ireland between August 1782 and May 1783 whilst his brother, Earl Temple, was Lord Lieutenant; Grenville was offered ministerial positions by his cousin Pitt the Younger throughout his premiership. Grenville was Paymaster General between December 1783 and March 1784 then he was appointed to the Board of Control for Indian Affairs. He was also instrumental in the negotiations that led to the Vergennes Treaty of 1786. For a short time in 1789 he was Speaker of the House of Commons, the youngest man to hold the post since the reign of Edward III in the Fourteenth Century; then he became Home Secretary. Grenville was created Baron Grenville of Wotton-under-Berhewood (Buckinghamshire) on 25 November 1790; in 1791 took over as Foreign Secretary. His own ministry lasted from February 1806 to March 1807.
When the French Revolution broke out, Grenville advocated British neutrality as the best means of avoiding conflict but when France declared war of Britain, Grenville supported the first coalition of European powers. He also supported repressive domestic legislation to maintain law and order in Britain. He resigned along with Pitt over the king's attitude towards Catholic Emancipation in March 1801, following the passing of the Act of Union with Ireland. However, he did not have confidence in Addington's abilities to conduct the war and spoke forcefully in opposition to the new government. He also abandoned Pitt, who did not respond to Grenville's proposal for a pact between the political "outs"; Grenville and Fox worked together in a combined Opposition. In 1804 when Pitt returned to power, Grenville refused to accept office without Fox. This completed the separation of the cousins.
When Pitt died, Grenville formed a ministry to continue the government and the fight against France: it became known as the 'Ministry of All the Talents'. Sidmouth was appointed as Home Secretary and Charles James Fox became Foreign Secretary - the first time that Fox had held office since 1783. However, Fox died in September 1806, which meant that the ministry had to be reconstructed. Grenville continued to support Catholic Emancipation and when the king refused to consider it as a measure, Grenville resigned. He spent the rest of his political career in opposition to the succeeding ministries of Portland, Perceval and Liverpool. However, it was his ministry that steered the Abolition of the Slave Trade legislation through parliament.
After the end of the French Wars in 1815, Grenville opposed the passing of the Corn Laws and supported the principles of free trade. He continued to support Catholic Emancipation but by 1822 he virtually had retired from politics. He suffered several strokes and died on 12 January 1834 at the age of 74.