Prior to the establishment of this province, its territory was part of the province of Pannonia Inferior. In 296 AD, Pannonia Inferior was divided into two separate provinces: Pannonia Secunda in the south and Pannonia Valeria in the north. The River Drava served as the border between the two newly created provinces.
The capital of Pannonia Secunda, Sirmium, held a prestigious status as one of the four capitals of the Roman Empire. Notably, several Roman emperors were born in or near this city, highlighting its significance in the empire's history.
In 314 AD, a pivotal battle took place between two rival claimants to the imperial throne, Constantine the Great and Licinius, in the province of Pannonia Secunda, near the town of Cibalae. Despite being outnumbered, with an army of 20,000 men against Licinius' 35,000, Constantine emerged victorious after a fierce battle that lasted the entire day.
As found in the Notitia Dignitatum. Provincial administration reformed and dioceses established by Diocletian, c. 293. Permanent praetorian prefectures established after the death of Constantine I. Empire permanently partitioned after 395. Exarchates of Ravenna and Africa established after 584. After massive territorial losses in the 7th century, the remaining provinces were superseded by the theme system in c. 640–660, although in Asia Minor and parts of Greece they survived under the themes until the early 9th century.