It begins at the port of Igoumenitsa and ends at Volos, passing through the towns Ioannina, Metsovo, Trikala and Larissa.

The EO6 is officially defined as a east-west route through central and northwestern Greece, between Volos in the east and Igoumenitsa to the west: the EO6 passes through Larissa, Trikala, Kalabaka, Mourgkani [el], Katara Pass, Metsovo and Ioannina.

[1] The EO6 west of Trikala is particularly mountainous, passing through the Pindus, and at Neraida [el], the EO6 briefly overlaps with the EO18.

The EO6, between Larissa and the interchange with the A3 motorway near Trikala, is being upgraded to dual carriageway with expressway characteristics.

Ministerial Decision G25871 of 9 July 1963 created the current EO6 from all or part of three short-lived national roads (listed from east to west), which existed by royal decree from 1955 to 1963: the old EO14 from Volos to Larissa; the old EO23 from Larissa to Ioannina; and the old EO26 from Ioannina to Igoumenitsa.