The Phocians, however, would not have formed an autonomous political entity, had they not faced the political pressure of the Thessalians, who managed to conquer Phocis in 595 B.C., during the First Sacred War. The reason was the fame and power that the sanctuary of Delphi (controlled, so far by the inhbitants of Krissa) had acquired meanwhile.  The control of the sanctuary would influence the political and military decisions which affected not only Greece but also all the Greek communities in the then known world.  Under Thessalian tutellage, the Phocians united and finally created a federal state, the Phocian League, with a common bouleuterion (To Phokikon)  and common coinage. All the cities had equal participation in the confederation.

There were 42 cities in total, of which the most important were 22: Lilaea, Erochos, Charadra, Elateia, Tithorea, Amphikleia, Drymaea or Drymon or Drymos, Teuthronion, Tritaea, Pedieia, Ledon, Avae, Yambolis (to the east, close to Boeotian Kephisus), Daulis, Panopeus, Phlygonio (in Elikon), Steiris, Ambrossos (on the south slopes of Parnassus, Krissa, Echedameia, Anemoleia (towards the region of the Ozolian Locrians) and the coastal cities Kirrha, Antikyra (possibly identified with the homeric Kyparissos), Medeon and Voulis.    

Furthermore, the towns Aeolidon Polis, Apollonias, Evenos (possibly close to Elateia), Eranos (possibly modern Kyparissi), Kirphis (close to Delphi), Kleonae (close to Yambolis), Lykoreia (high up on Mt. Parnassus), Marathos (close to the monastery of Hosios Loukas in Beoeotia)  Oghis, Trachis (close to Chaeroneia), Yapoia and Phokikon (south of Dauleia) are mentioned in ancient sources.

Elateia was the capital of the Phocian League. Coins were initially minted in Elateia, Lilaea, Antikyra and Ledon. Some of the aforementioned cities nowadays belong to Boeotia and some in Phokis, whereas Elateia, capital of the League, and Amphikleia, are situated in Phthiotis.

By looking at the catalogue of the cities which constituted the Phocian League, one is striken by the absence of Delphi. The fact is that the Phocians coveted the sanctuary and its incomes and they  thought that they should control it politically. Delphi, however, wanted to be autonomous. Several times, particularly within the 5th century B.C., the Phocians managed to gain control of the sanctuarly, particularly due to their alliances.

The main feature of the Phocian cities were their strong fortifications, dating mainly in the 4th century B.C. Yet, there are not many large and important public buildings. 

According to the ancient writers, the Phocians founded one important colony, namely Phocaea, on the Asia Minor shores, opposite to Chios. Its inhabitants became famous seafarers and founded colonies on the shores of France, the Iberian Peninsula, Corsica as well the Black Sea. Their most renowned colony is Marseille.

After Philip II finally established his supremacy in Greece, Phocis followed the fate of the rest of Greece.

Our best source for the history of Phocis  in the Byzantine period is the Chronicle of Galaxeidi, a narration of the  history of the city from the 10th to the 17th century, written in 1703 by the monk Euthymios. According to the Chronicle, in the course of the reign of Constantine Romanos (end oφ the 10th century), the area was raided by the Bulgarians. Many inhabitants were slaughtered or enslaved. The pest epidemic in 1054 caused a further demographic decrease. In eastern Phocis, on the other hand, in the mid-10th century lived Hosios Loukas, who became particularly famous.    The first little church where the saint was buried became soon a pilgrimage, which made the monk Philotheos ask for an imperial sponsorship in order to build a magnificent monastery which bears the name of the saint and is nowadays enlisted in the World Heritage List, as well as Delphi. For the construction of the monastery was used building material from the ancient city of Steiris.  

In the beginning of the 13th century, the Frankish king of Thessaloniki Boniface, Marquis of Montferrat, conquered Phocis and founded the County of Salona with Amphissa as its capital, which was renamed as La Sole. The first count of Salona, Thomas d’ Autremencour, built a strong castle on top of the ancient acropolis. After a short period of Byzantine reconquest (1210-1212), the region was subdued to the Principate of Achaia, whereas from 1278 onwards it passed under the control of the Duchy of Athens. When the latter was subjugated by the Catalan Company, in 1311, Phocis and Boeotia followed the same fate. In 1380 Phocis was conquered by the Navarraean Society, whereas in 1397 the Ottoman Turcs under Beyazid I invaded the region, invited by the local ruler, who wanted to get rid of the western tutelage, thinking that the Ottomans would maintain him in his position.  In 1402, after Beyazid’s defeat at the Battle of Ankara by Timur, the Ottomans receded and the region passed under the control of the Despote of Mystras, Theodore Palaeologos, who sold it to the Ioannite Knights. In 1410, however, the Ottomans came back and established once more their supremacy, which lasted for four centuries. 

In the course of the Ottoman period, the inhabitants of Phocis, a mountainous area not easily accessible, lived mainly off animal breeding and guarding the mountain passes. In 1580 the region suffered a severe earthquake, which destroyed a large part of the antiquities of Delphi, as well as the houses and fortifications of Amphissa and the surrounding region. Despite the relatively favourable status accorded to those guarding the mountain passes, or maybe even exactly because of their relatively autonomous state, serious revolts took place there, such as the one of 1687, when the monk Philotheos and captain Kourmas managed to drive away the Ottomans for a decade.

In the course of the 17th and, particularly, of the 18th and 19th centuries, several foreign travelers visited the region, mainly in order to admire and depict the archaeological site of Delphi. It is they who attempted at enhancing the antiquities and the history of the Phocian cities. To a certain extent they contributed to the national awakening of the inhabitants, who started looking back at their past with awe. Upon the outbreak of the Greek War of Independence, the Phocians responded immediately and on the 27th of March 1821 the people of Amphissa revolted under the leadership of Panourgias. On the 10th of April the castle of Salona was conquerred and its Ottoman defenders were killed. Many important leading figures of the revolution would surface in Phocis, such as the bishop of Salona Isaias, Panourgias, Dyovouniotis, Guras, Trakas, Athanasios Diakos etc. In 1826 Reshid Mehmed Pasha (known as  Kütahi), managed to get Salona back, but he finally surendered it to Dimitrios Ypsilantis in 1829. Many of the Ottoman public buildings, mainly the mosques, were demolished. A new destructive earthquake in 1870 accomplished the destruction of the Ottoman town, as not only the Ottoman buildings but also many of the town’s houses were demolished. The nearby village of Kastri suffered also severe damage, a fact which enabled the expropriation of properties and the initiation of excavations in the archaeological site of Delphi almost two decades  later.