Written history in the Sisak area was introduced by the Romany authors, and written materials are related to military operations in from the mid 2nd century B.C., which were led by the Romans in their attempt to conquer the fortified settlement of Segestica.

August Octavian finally conquered the fortified city in 35 B.C. The siege lasted for full 30 days and took two and a half legions to conquer the city. This introduced a new era in the history of Sisak. Roman Siscia developed on the left side of Kupa, in the area above which the older part of the modern city is located nowadays.

For the first several decades Siscia was an important military base but from the 1st century onwards, civilian significance of the town increases. The status of a colony was a granted to the town by the first emperor from the Flavian Dynasty, called Vespasianus (Colonia Flavia Siscia), probably in 71. The town was then inhabited by a large number of new inhabitants through the process of demilitarization of veterans from the Ravenna fleet, which was in proportion to the importance of the traffic on the river Sava towards Sirmij.

Once again the first emperor from the Severus Dynasty confirmed a high status of a colony, Septimius Sever in 194 (Colonia Septimia Siscia Augusta). By the end of the 2nd and beginning of the 3rd century, massive town ramparts were built of brick and fortified by stone. The remnants of these ramparts are clearly visible in front of today's parish church of the St. Cross. Numerous remnants of parts of decorated stone architecture permanently exhibited in the museum testify about the former look of the town. Remnants of the Roman material culture are numerous too, from various ceramic, metal, glass and bone objects for everyday use, jewellry, and military equipment to testimonies on funeral customs.

The town prospered in the first three centuries of the Roman rule. Abundance of shops and various craft shops were active as well as the river harbour. Emperor Gallienus (253-268.) established a coin in Siscia, which was used with several interruptions until the late 80's of the 4th century (according to some authors, even in the time of the emperor Honorius, i.e. until the 20's of the 5th century).

By the end of the 3rd century Siscia gained additional significance by becoming capital of the Savia province during the time of Diocletian. Diocletian's time was marked with great prosecutions of Christians in which the Bishop of Sisak Kvirin was killed (holiday of the saint-protector of today's Sisak, celebrated on 4th July). Late antiquity period, as well as the time when Christianity become a legal part of the Empire was documented by numerous objects belonging to the Sisak Museum.

The town was destroyed in the transit from 6th to 7th century, at least as far as the urban way of life is concerned.