The railway reached Pythion, known as Kuleliburgaz during Ottoman rule,[6] in 1873, when the line from Istanbul to Edirne and Bulgaria was opened.

During World War I, the railway was an important link for the transportation of troops and equipment, as the Ottoman Empire, Bulgaria, and Austria-Hungary were all Central Allies.

On 1 January 1971, the station and most of the Greek rail infrastructure was transferred to the Hellenic Railways Organisation S.A., a state-owned corporation.

Freight traffic declined sharply when the state-imposed monopoly of OSE for the transport of agricultural products and fertilisers ended in the early 1990s.

In Greece, a line was opened to allow trains from Pythion to Bulgaria to stay on Greek territory and avoid Edirne.

The station can be found in the 1957 novel From Russia With Love, the fifth novel by the English author Ian Fleming: Hot coffee from the meagre little buffet at Pithion, (there would be no restaurant car until midday), a painless visit from the Greek customs and passport control, and then the berths were folded away as the train hurried south towards the Gulf of Enez at the head of the Aegean.

However like in the novel, station is still housed in its original building, with a small buffet on site and remains the only cross-boarder rail route between Greece and Turkey.