On the morning of 17 February 1827, Lord Liverpool suffered a severe stroke which left him paralysed on one side. Irrespective of his very survival, his professional life was swiftly recognised as having come to an end. ‘[A]s an official man, he is no more’, Eldon reported to his daughter on the following day. The identity of Liverpool's successor, consequently, occupied the attention of the political world. The King was informed, and while he forbade any unseemly haste in replacing the stricken premier, the status quo could not long be maintained. After a period of intense speculation, meetings between ministers, and summonses to Brighton and Windsor, the King sent for the Foreign Secretary, George Canning. Canning was asked to form a government based on the same principles as those of his predecessor. He received his commission on 10 April. Within two days half the Cabinet had resigned, including Eldon, Robert Peel, and the Duke of Wellington. Thus collapsed a ministry that had governed for fifteen years, some of whose members had been in office far longer. For Eldon it was the end of almost thirty-eight years in government, with twenty-five of these spent as Lord Chancellor of England. In keeping with his long career of royal service, he alone of his colleagues tendered his resignation to the King in person.

The reasons for Eldon's resignation were several. First, he was nearly seventy-six years of age, and he had been speaking of retirement for some time.