The Thomas Paine was among the ships that met with Captain Picard at Dytalix B to discuss a possible alien conspiracy at work in Starfleet Command in 2364. (TNG: "Conspiracy")

In 2367, the Paine undertook a diplomatic mission to Epsilon Ashanti III. (TNG: "Brothers")

The Thomas Paine was assigned to Captain Picard's task force along the Kingon-Romulan Border during the Klingon Civil War of 2368. It served as a key component in Picard's tachyon detection grid. (TNG: "Redemption, Part II")

In 2386, the ship was one of the Federation vessels at the Battle of Bolarus. (TEM: "Blue Blood")