The prefecture was established after the death of Constantine I in 337, when the empire was split up among his sons and Constantine II received the rule of the western provinces, with a praetorian prefect as his chief aide. The prefecture comprised not only Gaul, but also of Roman Britain, Spain, and Mauretania Tingitana in Africa Proconsulare. Its territory overlapped considerably with what was once controlled by the short-lived Gallic Empire in the 260s.
After the permanent partition of the Empire in 395 into West and East spheres of control, the prefecture of Gaul continued to belong to the Western Roman Empire. Augusta Treverorum (present-day Trier in Germany) served as the prefecture's seat until 407 (or, according to other estimates, in 395), when it was transferred to Arelate (Arles).
The prefecture continued to function until 477, when the last areas under its control were seized by the Visigoths after the abolition of the Western imperial government of Ravenna in the previous year.
In 510, the Ostrogoth king Theodoric the Great re-established the prefecture in the small part of Gaul (the Provence) that he had just conquered, with headquarters again at Arelate. This short lived revival lasted until the area was in turn conquered by the Franks in 536, while the Ostrogoths were occupied by the East Roman invasion of Italy.