After campaigning against the foreign policy of the Beaconsfield ministry, William Ewart Gladstone led the Liberal Party to victory in the 1880 general election. The nominal leader of the Party, Spencer Cavendish, Marquess of Hartington, resigned in Gladstone's favour and Gladstone was appointed Prime Minister of the United Kingdom for a second time by Queen Victoria. He pursued a policy of parliamentary reform, but his government became wildly unpopular after the death of General Gordon in 1885. Gladstone was held responsible, and resigned, leaving the way free for the Conservatives under Robert Gascoyne-Cecil, 3rd Marquess of Salisbury to form a government.

†Created Earl of Selborne in 1882.

Cabinet members are listed in bold face.