The USS Thomas Paine (NCC-65530) was a Federation New Orleans-class frigate that was in service with Starfleet in the mid-24th century. During the early 2360s, it was commanded by Captain Rixx.

The Thomas Paine was one of the ships that met the USS Enterprise-D at planet Dytallix B when an alien intelligence attempted to take over Starfleet Command in 2364. (TNG: "Conspiracy")

According to a Starship mission status chart found in the Enterprise-D observation lounge, the Thomas Paine was on a diplomatic mission to Epsilon Ashanti III in 2367. (TNG: "Brothers")

In 2368, the Thomas Paine was assigned to Captain Jean-Luc Picard's fleet that blockaded the Klingon-Romulan border during the Klingon Civil War. The Thomas Paine was linked with the USS Ajax, USS Hood, USS Tian An Men, and USS Enterprise-D during the fleet's initial deployment of a tachyon detection grid along the border. Following the withdrawal of the USS Excalibur from the grid, the Thomas Paine was no longer linked with the Tian An Men. (TNG: "Redemption II")