In 1754, though still in office, he attacked his own Government, and was constrained to resign. But in 1756 Pitt was again in office as Secretary of State and leader of the Commons, under the Premiership of the Duke of Devonshire. In 1757 he was again out of office, but so strong was the confidence expressed by the public at large in the "Great Commoner," that he was soon back as virtual, though not nominal, Prime Minister. This was the celebrated four years during which Pitt's life has been called the history of England. It was he that chose General Wolfe, and so brought about the taking of Quebec; his encouragement of Clive "led to the founding of our Indian Empire ; and by his aid Frederick the Great ended the Seven Years' war. With the accession of George III. and the advent of Lord Bute to office arose difficulties, especially that of the Bourbon League, which led to Pitt's retirement, and he accepted a pension of £3,000 a year, and a peerage for his wife.
In 1766 he supported the bill for repealing the American Stamp Act, and in the autumn of that year he was entrusted by the king with the formation of a ministry. With its formation he went to the Upper House as Viscount Pitt and Earl of Chatham - a step which cost him much in popularity. At this point of his career, just when a most critical juncture had arisen, especially with regard to the American question, a mysterious illness utterly incapacitated him for business, and the Ministry were virtually without a head. He remained in retirement, and in 1768 he resigned on the ground of ill-health. In 1770 he appeared again in the House of Lords as the opponent of the Government on their American policy; and in 1778 he spoke for the last time against concluding a peace. The famous historical picture has made everyone acquainted with the details of this scene, and how the stricken peer was removed from the House to die the next month at Hayes. The great defect in Chatham's political career seems to have been the inconsistency with which he changed his opinions when the change brought power. In this he is not without later imitators.