He studied in Paris and in Munich. In 1905, he was elected to the Hellenic Parliament from Karditsa prefecture. In 1909, he served as Foreign Minister under Dimitrios Rallis. After the First Balkan War, he was appointed Governor General of newly-liberated Northern Epirus by PM Eleftherios Venizelos.
Christakis-Zografos served as Governor General of Northern Epirus from March 29 (March 16 OS), 1913 until December 31 (December 18 OS) of the same year. When the Great Powers decided to award Northern Epirus to Albania, local Greeks formed a provisional government under Christakis-Zografos on February 16, 1914 and declared their independence the following day in Argyrokastro.
Eventually, political pressure by the Great Powers on Greece brought the Northern Epirus state to an end.
Christakis-Zografos served as Foreign Minister of Greece between February 25 and July 5, 1915 in the government of Dimitrios Gounaris. He favoured involvement in World War I and resigned in frustration when his views were disregarded.