In 2377 the Independence was sent to investigate an unusual subspace phenomenon inside the Briar Patch however it disappeared before any information could be gathered. (Star Trek: Hidden Frontier: "Two Hours")
- In an alternate timeline the ship entered the vortex and was sent back in time to Earth on the night of the sinking of the RMS Titanic where it was discovered the ship's destruction was caused by intervention from the 29th century.
On Stardate 60423.8, the USS Independence was escorting transports through the Briar Patch when she came under attack from the Tholians. Under the orders of Rear Admiral Jennifer Cole, all of the Independence's shuttle and attack craft were launched in an attempt to counter the onslaught but to no avail. Cole ordered the ship abandoned, herself escaping with the bridge crew on the captain's yacht. The wreckage of the ship was discovered by the USS Angelfire, while it conducted the search and rescue operation. (Star Trek: Hidden Frontier: "Hearts and Minds")
In different continuities the Independence has different registries:
|USS Advantage - USS Alhambra - USS America - USS Argus - USS Anne Frank - USS Beast - USS Behemoth - USS Black Hawk-A - USS Challenger - USS Dauntless - USS Edmund Fitzgerald - USS Enterprise-E - USS Excelsior - USS Federation - USS Freedom - USS Gibraltar - USS Grissom - USS Hawk-A - USS Honorius - USS Incipiens - USS Independence - USS Khitomer - USS Kyle Fitzgerald - USS Liberty - USS Monarch - USS Pir - USS Prince of Wales - USS Protector - USS Ravana - USS Saratoga - USS Sathanas - USS Sovereign - USS Violet Baudelaire - USS Yagami - USS Zephyra|
|Starfleet International: USS Black Hawk - USS Chicago - USS Protector - USS Silver Moon - USS Sovereign - USS Wildhorse|
|Mirror universe: Enterprise|