It has been identified with extensive ruins south of Shahabad, a village 14 km south-east of Dezful, to the road for Shushtar, in the present-day province of Khuzestan, southwest Iran.

Ya'qub ibn al-Layth al-Saffar, the founder of the Saffarid dynasty, made Gundeshapur his residence three years before his sudden death in 879.

The city, constructed as a place to settle Roman prisoners of war, subsequently became a Sasanian royal winter residence and the capital of the Khuzistan province.

[7] Most scholars believe Shāpur I, son of Ardeshir (Artaxexes), to have founded the city after defeating a Roman army led by Emperor Valerian.

In 489, the Nestorian theological and scientific center in Edessa was ordered closed by the Byzantine emperor Zeno, and transferred itself to become the School of Nisibis[9] or Nisibīn, then under Persian rule with its secular faculties at Gundeshapur, Khuzestan.

[10] It was under the rule of the Sassanid monarch Khusraw I (531-579 CE), called Anushiravan "The Immortal" and known to the Greeks and Romans as Chosroes, that Gundeshapur became known for medicine and erudition.

In addition, the intellectual center of the Abbasid Caliphate had shifted to the Arab stronghold of Baghdad, as henceforth there are few references in contemporary literature to universities or hospitals at Gundeshapur.

Gundeshapur had been major link between Indic and some Greek medicine, because of its previous practices of combining the medical traditions, therefore the transition from earlier ancient civilisations to later Islamic appropriation was more coherent.

Ath-Tha'ālibi, a scholar with access to Sassanian royal annals, discussing pre-Islamic Persia, wrote: Thus, the people of Sūs [Susa] became the most skilled in medicine of the people of Ahwāz and Fārs because of their learning from the Indian doctor [who was brought to Susa by Shāhpūr I] and from the Greek prisoners who lived close to them; then [the medical knowledge] was handed down from generation to generation.