Originally based in Smyrna/Izmir, the club was uprooted in the population exchange between Greece and Turkey following the Asia Minor Catastrophe in 1922.

It is now based in the suburban town of Nea Smyrni, located in the Attica, and where many of the refugees from Smyrna settled.

Panionios has a long tradition of raising talented athletes in many sports (e.g. Fanis Christodoulou, Thomas Mavros, Nikos Anastopoulos, Dimitris Saravakos, etc.)

The name related with the legendary musician of ancient Greece, because the main activity of the club was the music.

[2][3] In 1896, Gymnasium organized the first Panionian Games and in 1897 participated in the foundation of SEGAS along with 25 clubs from Greece and two from Cyprus.

Thanks to Chrysostomos of Smyrna,[citation needed] Panionios was allotted a big area for its gymnasium near the Greek cemetery.

In November 1937, Panionios Board of Directors led by President D. Karabatis and the Municipality of Nea Smyrni agreed to relocate the club in Nea Smyrni, the Athens suburb that was mainly inhabited by Greek Asia Minor refugees coming from Smyrna, the club's historical home.

The next year it was the runner up of the Football Cup where defeated by Olympiacos in the replay game (the first match had finished 2-2).

Panionios football team evolved to one of the protagonists of Greek championship with steady presence in first division.