Canning's father, the eldest son of an Irish landowner, was disinherited for his marriage to a beautiful but penniless girl and died in 1771, leaving his wife and year-old son entirely destitute. The widow became an actress and the mistress of an actor, and in 1783 she married another actor. From this unsatisfactory environment, George Canning was taken away by a wealthy uncle, Stratford Canning, who raised him with his own children, one of whom was the future diplomat Viscount Stratford de Redcliffe.

Canning was educated at Eton College and at Christ Church, Oxford. After graduating (1791), he soon decided on a political career and, in July 1792, came under the influence of the prime minister, William Pitt (Pitt, William, The Younger), who undertook to find him a seat in Parliament. He was elected for the privately controlled borough of Newtown, Isle of Wight, in July 1793 and quickly became recognized as one of the rising men on the government side of the House. Pitt further procured for him the undersecretaryship of state for foreign affairs in 1796.

In 1799 he left the foreign office and was appointed a commissioner of the Board of Control for the government of India. In May 1800 he was promoted to the office of joint paymaster of the forces and was made a privy councillor. A few weeks later he married an heiress, Joan Scott. With her he had four children, including Charles John, later Earl Canning and a governor-general of India.

When Pitt resigned in 1801, Canning, too, left office. On the formation of Pitt's last ministry in May 1804, Canning became treasurer of the navy, but his unpopularity (his biting wit made him many enemies) kept him out of the cabinet. Much to his disgust, his colleagues resigned after Pitt's death (January 1806) because of the insecurity of their parliamentary position. When, however, in March 1807 the king called upon “the friends of Mr. Pitt” again to form a government, Canning became foreign secretary.

Actions in the Napoleonic Wars that occurred during Canning's first tenure of the foreign secretaryship included the seizure of the Danish fleet (his own brilliant planning) and the unfortunate expedition to Walcheren Island off the Schelde River, in The Netherlands. The Peninsular War, involving British, Spanish, and French resistance to Napoleon on the Iberian Peninsula, was also begun. Holding Viscount Castlereagh (Castlereagh, Robert Stewart, Viscount), the war secretary, responsible for the disasters that overtook British arms at Corunna in Spain, and at Flushing (Vlissingen) in Holland, Canning in 1809 insisted on his dismissal. They quarreled and fought a duel on September 21, in which Canning was wounded in the thigh. Both had already resigned, Canning because of the nonfulfillment by the Duke of Portland, William Bentinck, the dying prime minister, of his promise that Castlereagh should be removed from the War Department. Canning offered to form a government, but the king called upon his rival, Spencer Perceval, and Canning remained out of office until 1816.

Lord Liverpool, who succeeded to the prime ministry in 1812 on Perceval's assassination, tried hard to induce Canning to take office, but Canning refused to allow his old rival Castlereagh (who generously offered to surrender the foreign secretaryship to him and to take the inferior office of chancellor of the Exchequer) to retain the leadership of the House of Commons. So Canning lost the chance of being the peacemaker of Europe in 1815.

Two years later, he entered the cabinet as president of the Board of Control. Canning, disapproving of the government's efforts to deprive George IV's (George IV) queen, Caroline (Caroline of Brunswick-Lüneburg), of her title and position, resigned in December 1820. In the hope of improving his financial position and believing that advancement at home was blocked by the king's hostility to him, he accepted the governor-generalship of Bengal in March 1822, with the additional prospect of a peerage on his return, but, before his ship was ready to sail, Castlereagh committed suicide (August 12), and George IV reluctantly acquiesced in Canning's succession to the “whole inheritance”—the foreign secretaryship and the leadership of the House of Commons.

He was now the most important member of the government. Afraid of becoming too deeply involved in continental politics and disliking the great despotic sovereigns who were anxious to suppress liberal movements everywhere, he cut England adrift in 1823 from the so-called Holy Alliance engineered by the emperor Alexander I of Russia to preserve the European status quo. He prevented France from intervening on the side of Ferdinand VII when that monarch sought to subdue revolts in Spain's colonies in South America. Canning then recognized the independence of the rebellious Spanish-American colonies and so, in his famous phrase, “called the New World into existence to redress the balance of the Old.” He also sent an army to Portugal to meet the threat of attack by Spain, gave diplomatic support to the Greeks in their struggle with the Turks for freedom, and ensured the eventual creation of an independent Greek state.

Lord Liverpool's premiership came to an end in February 1827. He had long since marked out Canning as his successor, but it was far from obvious that Canning would be the king's choice. Since 1822 Canning had gained a remarkable ascendancy at Windsor Castle by the success of his foreign policy and by a judicious attention to the royal intimates there. But he was also the leading advocate of Roman Catholic Emancipation, and George IV had been persuaded that the cause of the monarchy was linked with that of the established church and resistance to Catholic claims. Robert Peel and the Duke of Wellington, the leading opponents of Catholic relief, knew that no government could be formed without Canning, and Canning refused to serve under another anti-Catholic prime minister.

Finally, on April 10, he was authorized to reconstruct the ministry on the understanding that a Catholic relief bill was not to be forced on the king. Moved partly by personal animosity and partly by dislike of Canning's advocacy of Catholic emancipation, half the cabinet refused to serve under him, and, in all, more than 40 Tory ministers and political appointees resigned. The Whigs, however, came to his assistance, and most of the independent members of Parliament supported him with their votes. But his ministry lasted only four months; his health broke down under the strain, and he died in August 1827 at Chiswick, in the house of the Duke of Devonshire.

The hatred and malignity with which Canning was assailed by the Tory aristocracy in 1827 showed what prejudice still existed against a prime minister born outside the governing class. Contemporaries said that Canning's ministry was the most popular with the middle classes that had ever been known. As member for Liverpool (1812–22), he came to recognize fully the needs of the rising commercial and industrial interests. Canning helped the Tory Party take a more liberal view on many questions of domestic, colonial, and foreign policy. Although a steadfast opponent of parliamentary reform, he helped contribute to the creation of that independent and liberal spirit among the younger members of the House of Commons without which the Reform Bill of 1832 could not have been carried without a revolution. Lord Granville said that Canning “sought to avoid revolution, not by stubborn resistance to all movement and reformation, but by rendering the acts of the government conformable to the spirit of the times.”