One account says that the city was named after the mythological figure of Lamia, the daughter of Poseidon and queen of the Trachineans.

In the Middle Ages, Lamia was called Zetounion (Ζητούνιον), a name first encountered in the 8th Ecumenical Council in 869.

It was known as Girton under Frankish rule following the Fourth Crusade and later El Citó when it was controlled by the Catalan Company of mercenaries.

[5] In antiquity, the city played an important role due to its strategic location, controlling the narrow coastal plain above Thermopylae that connected southern Greece with Thessaly and the rest of the Balkans.

In Late Antiquity, the city was the seat of a bishop (attested since 431), suffragan of Larissa,[7][8] but had declined to obscurity: for instance, it is not shown on the 5th-century Tabula Peutingeriana.

[9] The city was occupied by Slavs in the 7th century, and re-appears only in 869/70 under the name of Zetounion (Ζητοῦνιον), probably deriving from a Slavic word for "grain".

[5][7][8] The city played once more a role in the Byzantine–Bulgarian wars of the late 10th century due to its vicinity to Thermopylae: it was near the town that the Byzantine general Nikephoros Ouranos scored a crushing victory over Tsar Samuel of Bulgaria in the Battle of Spercheios in 997.

The Latin Emperor Henry of Flanders confiscated the city (and neighbouring Ravennika) and made it an imperial domain under a bailli, possibly Rainerio of Travale.

[10] Under Frankish rule, it was the seat of a Roman Catholic bishop (Dioecesis Sidoniensis or Cythoniensis), probably a suffragan of the Latin Archbishop of Neopatras.

[5][11][12] Lamia remained in Greek hands until it was surrendered again to the Franks of the Duchy of Athens in 1275 as part of the dowry of Helena Angelina Komnene, daughter of John I Doukas, ruler of Thessaly.

[8][14] After the disastrous Battle of Ankara in 1402, the weakened Ottomans were forced to return some territories, including the region of Zetounion, to Byzantine rule.

[15] Apart from an attack by the troops of the Despotate of the Morea in 1444, which plundered the city,[14] from then on the town remained under firm Ottoman control until it became part of the newly independent Kingdom of Greece in 1832.