The Federation flagship for over 8 years, the Enterprise-D was one of the first Galaxy-class starships to enter service, being commissioned in early 2364 under the command of Captain Jean-Luc Picard. With a crew complement of a little over a thousand people, including civilians and children, the Enterprise-D was a self sufficient city in space.

The ship was capable of separating its primary hull from the rest of the ship. This allowed the civilian population to remain safe while the secondary hull, which housed most of the weapons and power systems, engaged in any dangerous mission. This saucer separation however proved to be a time consuming affair, which was often at odds with the fast response needed in a crisis situation. Because of this, in practice it was seldom used.

The ship's successful career was cut short in 2371. Just after receiving a major refit, the ship was attacked over Veridian III by a renegade Klingon ship under the command of the Duras sisters. While Enterprise was victorious in the end, its warp core had sustained enough damage that a breach was inevitable. The crew managed to escape to the saucer section and separate the ship, but the warp core explosion pushed the saucer into the Veridian III gravity well, where it crash landed. Casualties were low among the crew, which was eventually rescued by starships Farragut, Brattain, and Trosper.

Though the ship was deemed lost to Starfleet, the saucer section was retrieved from Veridian III, as its eventual discovery by the pre-warp Veridian IV natives would disrupt their natural course of development. By the 2390's the Starfleet Museum started restoring the Enterprise-D. The interior was returned to its pre-refit look; and the secondary hull was replaced by that of the USS Syracuse.