As the events of the First World War were unfolding on various fronts, the problem of coalition between the Great Powers and the Balkan countries was pressing.

As the objective was to win over Bulgaria, the cessation of Greek territories in eastern Macedonia was proposed. This proposal was put forward both by the Allies, who had proposed to Greece territorial exchanges in Asia Minor in return, and later by the Central Powers, with which Bulgaria finally aligned and captured eastern Macedonia. The question of ceding Greek territories to Bulgaria exacerbated the relations between the Venizelists and the Constantinists. From both sides accusations of treason were launched, according to adherence to one or other international league (Entente or Central Empires) and to plans for the capture of the area by the Bulgarians.

In 1915 Venizelos openly supported the coalition with the Entente. The allied operations in the peninsula of Gallipoli against Turkey served as a pretext. The Prime Minister proposed the participation of Greek troops in these operations. He thus encountered strong opposition from the King. This conflict led to the resignation of the Prime Minister. Venizelos, regaining power after the elections of summer 1915, and in the face of Bulgaria entering the war and its attack on Serbia, gave orders for mobilization. The desicion was nominally ratified by Constantine. At the same time Entente forces landed and took control of Thessaloniki. When the Prime Minister Venizelos brought forward the matter of active participation, he was once more led to resignation. There was again his fundamental disagreement with Constantine, who did not wish to confront Germany at any cost. The Venizelists, however, held the majority in Parliament and their foreign policy was endorsed by the people's vote.

The capture of eastern Macedonia and the city of Kavala by the Bulgarian army, the emprisonmnet of parts of the Greek army and the persecutions of the Greek population in the summer of 1916 rendered more acute the clash between the two camp vis-a-vis the international conflict. Eleftherios Venizelos decided to side with the movement of the National Defence and formed a revolutionary government in Thessaloniki, declaring war on the Central Powers and, naturally, Bulgaria.