Although largely unchanged since the 1960s, it remains the largest and busiest railway station built in Greece and one of the country's most important works of modern architecture.

The architectural tender for the new railway station, to replace the now outdated Old Thessaloniki railway station was announced in 1935[14] construction began 26 October 1937[14][15] following an international architectural design competition that was carried out at the time and won by German architect Hans Kleinschmidt, a notable runner-up was Nikolaos Mitsakis.

[15] In 1958, the project was restarted, headed by Greek architects Molfesi and Papagianni, who made changes to the original design by Kleinschmidt, with a more modernist style.

Electrification was installed in the 1990s with the assistance of the Romanian Railways, and in 1998 the first electric services started to Gevgelija using a leased CFR Class 41 locomotive of the Brașov depot.

[18] In 2003, OSE launched "Proastiakos SA", as a subsidiary to serve the operation of the suburban network in the urban complex of Athens during the 2004 Olympic Games.

The station has remained largely unchanged since that time, although minor additions have occurred, such as the construction of a shopping centre adjacent to the waiting hall and the installation of escalators for access to the platforms.

[20] In February 2011, the station suffered a loss of importance given the suspension of all rail links to international destinations.

[25] In November 2023, rail services resumed between Rapsani and Larissa after a devastating storm in September[26] damaged sections of track across the region.

The station currently features large waiting areas, a central hall with cafes,[28] restaurants, a small chapel and a shopping centre within a 1960s era building.

Discussions are underway for the expansion of the station and a general overhaul, which will also include a hotel and a revamp of the central offices of the OSE for northern Greece.

[5] The station is served the following Hellenic Train services: Note: Between July 2005 and February 2011, the Friendship Express, (an international InterCity train jointly operated by the Turkish State Railways (TCDD) and TrainOSE linking Istanbul's Sirkeci Terminal, Turkey and Greece terminated at Thessaloniki railway station.