Originally built in the colonial style, with a strong romantic stamp, the building was almost identical to that of Volos, both of which stood out for their aesthetic apprentice.

In March 1889, the government of Charilaos Trikoupis ordered the construction of The "Piraeus-Demerli-Border Railway"[12] and a second station was built to 1,435 mm (4 ft 8+1⁄2 in) standard gauge.

[11] On 8 March 1957, Thessaly was hit by a 6.4 doublet earthquake[12] while reported casualties were light, much of Evaristo de Chirico station buildings, suffered severer damage and were deemed unsalvageable.

The major reconstruction meant most of the old Thessaly Railways station still standing was demolished with the construction of the existing one began in 1960.

[15] 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.

In 2011 it was reported that the Greek government was looking at divestiture of certain high-profile assets of OSE, namely a number of the larger terminal stations, most notably Athens, Piraeus, Thessaloniki, Volos and also Larissa.

[17] In 2017 OSE's passenger transport sector was privatised as TrainOSE, (Now Hellenic Train) a wholly owned subsidiary of Ferrovie dello Stato Italiane.

In February 2021, severe weather closed the network around Larissa, with stations inaccessible, and overhead power lines down, leading to delays of over 12 hours.

[33] OSE engineers were on the ground in the worst affected areas Domokos, Doxaras, and Paleofarsalos to assess the extent of the damage, and prepare detailed reports, and seek financial assistance from the European Union.

[36] OSE managing director, Panagiotis Terezakis, spoke of reconstruction works reaching 50 million euros, confirming at the same time that there will be no rail traffic in the effected sections of the network for at least a month.

[37] The devastation goes beyond the tracks and signalling, affecting costly equipment such as the European Train Control System (ETCS), which enhances rail safety.

However services between Larissa and Volos remain suspended across Thessaly’s coast until the track is repaired, with a rail-replacement bus in operation.

On 8 March 2008, an Alexandroupolis-bound[52] InterCity train derailed 2 kilometres (1.2 mi) outside the station, with Reuters reporting no deaths and a total of 28 people injured in the incident.

Initial reports indicate an unknown person in the control room had switched the points, sending the train straight into the building.

[56] On 26 April 2019, two carriages on an Intercity service between Thessaloniki and Athens derailed outside Larissa; no injuries were reported among the passengers.