- William T. Riker is offered command of the ill-fated USS Drake, but instead accepts posting to the new USS Enterprise-D as first officer. (TNG: "The Arsenal of Freedom")
- Captain Jean-Luc Picard takes command of the USS Enterprise-D and the ship departs Earth on its first mission, to Farpoint Station. The official order to take command is signed by Rear Admiral Norah Satie on stardate 41148. The Enterprise subsequently makes first official contact with the Q entity and the lifeform which formed Farpoint. (TNG: "Encounter at Farpoint", "All Good Things...")
- The Enterprise receives a strange message from the crew of SS Tsiolkovsky, an Oberth-class vessel observing a red supergiant that is about to explode into a white dwarf. Upon arrival, the crew is discovered all dead by an away team. The crew of the Tsiolkovsky was suffering from polywater intoxication, which is later introduced to the Enterprise crew by Geordi La Forge. The Enterprise is nearly destroyed by a stellar core fragment from the supergiant after Jim Shimoda removes all the isolinear chips from engineering, preventing the Enterprise from going to warp, but the ship is saved by the actions of Lieutenant Commander Data and Wesley Crusher. (TNG: "The Naked Now")
- The Enterprise-D travels to Ligon II to acquire a vaccine for Anchilles fever that afflicted the population of Styris IV from the Ligonians. (TNG: "Code of Honor")
- The Enterprise is hurled to the M-33 Galaxy by the Traveler. (TNG: "Where No One Has Gone Before")
- The Enterprise makes first official contact with the Ferengi. (TNG: "The Last Outpost")
- The USS Stargazer, Picard's first command, is returned to Starfleet custody by the Ferengi. (TNG: "The Battle")
- Starfleet Admiral Mark Jameson dies on Mordan IV. (TNG: "Too Short a Season")
- Lore is discovered on Omicron Theta by the Enterprise crew. He is reassembled, but later transported into space when he tries to betray the Enterprise to the Crystalline Entity. (TNG: "Datalore")
- The star Beta Magellan goes supernova. Computer systems on the planet Bynaus, which is close by, are destabilized. The Bynars temporarily hijack the Enterprise-D from Starbase 74 in order to repair their damaged computers. (TNG: "11001001")
- First contact made after discovering the existence of the microbrains of Velara III, who had been attempting contact themselves. They request to be left alone for three centuries and would consider re-opening communications with the Federation in 2664. (TNG: "Home Soil")
- The mythical planet of Aldea is revealed to exist. (TNG: "When The Bough Breaks")
- Natasha Yar is killed on Vagra II by the entity known as Armus. (TNG: "Skin of Evil")
- Neural parasites infiltrate Starfleet Command. Admirals Gregory Quinn and Norah Satie are instrumental in uncovering the alien plot, Dr. Beverly Crusher discovers a means of removing the parasites from the host, and Captain Picard and Commander Riker destroy the mother creature. The parasites transmit a homing message before they are killed. (TNG: "Coming of Age", "Conspiracy", "The Drumhead")
- Several Federation and Romulan outposts close to the Neutral zone are destroyed prior to and on stardate 41903.2. Both the Federation and the Romulans suspect each other as the cause. (TNG: "The Neutral Zone") Based on similarities with other attacked stations (TNG: "Q Who", "The Best of Both Worlds"), it is probable these events marked the first appearance of the Borg in Federation space during the 24th century.
- The Romulan Star Empire returns to interstellar politics after 53 years of isolation. (TNG: "The Neutral Zone")
- Senator Pardek represents Romulus on a Barolian trade conference. (TNG: "Unification I")
- Aamin Marritza started to work as an instructor at the Cardassian Military Academy on Kora II. (DS9: "Duet")
- Morn visits Quark's for the first time. (DS9: "Who Mourns for Morn?")
- The Bajoran Ro Laren graduates from Starfleet Academy and is assigned to the USS Wellington. (TNG: "Ensign Ro")
- The Jem'Hadar Virak'kara is created in the Gamma Quadrant. (DS9: "To the Death")
- Mardah leaves her foster family on Bajor to live on her own. (DS9: "The Abandoned")
- A few weeks before the USS Enterprise-D visited the Vandor system, there is an accident in one of the labs of the research outpost on the fourth planet. There are two survivors - Dr. Paul Manheim and his wife, Jenice. (TNG: "We'll Always Have Paris")
- Six months before the starship Enterprise-D visited the Omega Sagitta system, Benzan of Straleb and Yanar of Atlec begin courting each other with the assistance of Captain Thadiun Okona. (TNG: "The Outrageous Okona")
- Starfleet begins a search for a suitable star which will meet the requirements, including its similarity to the Kaelon II sun, for a test of the helium fusion enhancement. (TNG: "Half a Life")
- The year 2364 is given by Data on screen in "The Neutral Zone", and is the first specific on screen date given in Star Trek. This year serves as the fixed reference around which subsequent timeline data was placed. Prior to this, fandom had generally placed Star Trek: The Next Generation in the early 24th century.
- "All Good Things..." (in part)
- "Encounter at Farpoint"
- "The Naked Now"
- "Code of Honor"
- "Where No One Has Gone Before"
- "The Last Outpost"
- "Lonely Among Us"
- "The Battle"
- "Hide and Q"
- "Too Short a Season"
- "The Big Goodbye"
- "Angel One"
- "Home Soil"
- "When The Bough Breaks"
- "Coming of Age"
- "Heart of Glory"
- "The Arsenal of Freedom"
- "Skin of Evil"
- "We'll Always Have Paris"
- "The Neutral Zone"
- In the game Star Trek: Armada, a Borg sphere arrives from 2376 to destroy the Enterprise-D and kill Picard, to prevent a Borg defeat in that time period. Seconds later, the USS Premonition arrives to destroy the sphere. Succeeding, it immediately returns to 2376 to prevent any further contamination to the timeline. Captain Picard remembers this encounter, and no further reference is heard about this encounter until 2376 where he states he has seen the ship before.