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This well-forested region attracted inhabitants from the surrounding lowlands after the Ottoman conquest. On the slopes of the verdant Pindos Mountains, thriving hamlets sprouted, which over the centuries welcomed new settlers, mainly Vlachs.

The terrain dictated the citizens' occupations (stock breeders and muleteers cum merchants) and made the area a junction for communications between Macedonia, north-west Thessaly and Epirus, as can be seen from the stone bridges and traces of roads that have survived.

During the 16th century the area was involved in revolutionary activity; in 1537 the first reference is made to the armatoliki of Grevena, where the legendary Kapetan Vergos was based. (An armatoliki was a settlement given special privileges by the Turks, including the right to bear arms.)

The region was subjected to mass conversions to Islam in the late 18th century, when formerly Christian villages are mentioned as having a purely Muslim population. Despite the actions of the armatoles (e.g. Yero-Ziakas) and the initiation of many of them into the 'Philiki Etaireia', the area was not in a position to prepare itself for the revolution of 1822.

Cut off from their own armatolikia, many warriors joined other revolutionary bands, while Theodoros Ziakas played a leading role in the uprising of 1854. A place of conflict between guerrilla bands as early as 1897 , as well as during the Macedonian Struggle, the region of Grevena was liberated during the First Balkan War.