[4] The original structure was built during 1842 as a house for Antonis Dimitriou, a wealthy Greek businessman from the island of Lemnos, twelve years after independence of Greece from the Ottoman Empire.

In 1874, it was bought by Efstathios Lampsas, who restored it with an 800,000 drachma loan and named it "Grande Bretagne."

On Christmas Day of 1944 and shortly after the events of the Dekemvriana during which the British military alongside Greek collaborationists fired on civilians in Athens, members of the EAM guerrilla resistance organization, including resistance hero Manolis Glezos, planted dynamite in the sewers of the hotel in an attempt to blow up the British headquarters and assassinate General Scobie.

The attack was however called off when EAM leadership learned that Winston Churchill had arrived, who had traveled to Greece in an attempt to broker peace between the opposing Greek factions, the UK having previously been allied with the Greek resistance movement against the Axis powers.

In January 2023, the hotel housed numerous European royals who were arriving in Athens the funeral of Constantine II of Greece.