The USS Rome was commissioned in 2370 and placed under the command of Captain Ian Boswell. The Rome spent the next three years exploring in deep space, even obtaining permission from the Tholian Government to explore their space, provided they were escorted.

In 2373 the Rome was re-assigned to the Federation-Klingon border as a border defense ship after the Klingons dissolved the Khitomer Accords and attacked Cardassia Prime. The Rome was one of the first ships to be dispatched to Deep Space Nine when the Dominion War began. However, the Rome was diverted away from DS-9 after the Federation withdrew from the base.

During the Dominion War the Rome participated in the battle to reclaim Deep Space Nine and the Battle of Chin'toka. At the Battle of Chin'toka Captain Boswell was killed and Commander Stovak assumed command of the Rome. It was a command he would keep until Commander Malkus took command of the Rome following Stovak's re-assignment to the USS Tempe as commanding officer.