[1] It connects the Greek National Road 2 at Diavata, a northwestern suburb of Thessaloniki, with Kilkis.

Most of the National-Road has been upgraded to a Motor-Road, connecting Thessaloniki via Kilkis with Doirani, the eastern border of Greece and North Macedonia.

The Road will be constructed as a Motor-Road, the part Nea Santa until Kilkis are ready, the second part after Kilkis will be constructed until 2014.

Ministerial Decision G25871 of 9 July 1963 created the EO65 from the short-lived EO39 from 1955.

[2][3] In 1998, the Hellenic Statistical Authority extended the EO65 designation from Kilkis to Petritsi via Mouries, taking over some of the Kilkis regional unit's Provincial Roads.