With 24 decks, it was equipped with the latest in equipment and defenses, including quantum torpedoes. It did not go into full service immediately, even for shakedowns. By stardate 50893.5 the ship had only been in space and fully crewed for nearly a year. Having plunged into a temporal wake near Earth created by invading Borg, it followed the Borg back to the twenty-first century and stopped them from preventing Zefram Cochrane's pioneering warp drive test and first contact with the Vulcans.
Enterprise-E was on the front lines again, when the Son'a threatened the Bak'u with their plans to rob the Bak'u homeworld of its metaphasic radiation, for the radiation had fountain-of-youth-like properties.
During its most recent mission, the ship suffered severe damage during an encounter with Shinzon, the ruthless Reman/Picard clone, and his warship, the Scimitar. The ensuing battle resulted in Picard putting Enterprise on a collision course with the Scimitar, forcing the Federation flagship to put into drydock following the skirmish.