Charles was educated at Charterhouse School and University College, Oxford, where he graduated M.A. in 1752. In 1761 he entered parliament as member for Cockermouth and was made Under-Secretary of State by Lord Bute; he won the favor of George III, and when Bute retired Jenkinson became the leader of the King's Friends in the House of Commons. In 1763 George Grenville appointed him joint Secretary to the Treasury; in 1766, after a short retirement, he became a Lord of the Admiralty and then a Lord of the Treasury in the Grafton administration; and from 1778 until the close of Lord North's ministry in 1782 he was Secretary at War. From 1786 to 1803 he was President of the Board of Trade and Chancellor of the Duchy of Lancaster, and he was popularly regarded as enjoying the confidence of the king to a special degree. In 1772 Jenkinson became a Privy Councillor and Vice Treasurer of Ireland, and in 1775 he purchased the lucrative sinecure of clerk of the pells in Ireland and became Master of the Mint. In 1786 he was created Baron Hawkesbury and ten years later Earl of Liverpool. He died in London on 17 December 1808.
Liverpool was twice married: first to Amelia (d. 1770), daughter of William Watts, governor of Fort William, Bengal, and secondly to Catherine, daughter of Sir Cecil Bisshoff, Bart., and widow of Sir Charles Cope, Bart. He had a son by each marriage. His eldest son, Robert, was to become a prominent politician and eventually Prime Minister of the United Kingdom. Liverpool wrote several political works but except his Treatise on the Coins of the Realm (1805) these are, according to the 1911 Encyclopædia Britannica, "without striking merits."