When the Great Powers decided to award Northern Epirus to Albania, local Greeks formed a provisional government under Christakis-Zografos on February 28, 1914 and declared their autonomy the following day in Gjirokastër.

However, this state was short lived and on October 27, when World War I broke out and the Albanian government collapsed, the Greek army re-entered the area with the sanction of the Great Powers.

A little while later he became executive of the National Bank of Greece, position he retained until September 1917, with a short-term interval (February 25-August 10, 1915) when he became for second time Minister of Foreign Affairs under the cabinet of Dimitrios Gounaris.

He supported the entrance Greece on the side of the Triple Entente during World War I, foreseeing that this strategic move could offer to the country several advantages.

During the Communist regime in Albania (1945–1992), Georgios Christakis-Zografos and his father Christakis Zografos (notable benefactor and entrepreneur), were stigmatised as 'enemies of the state'.