- Captain Kirk assumes command of the USS Enterprise for an historic five-year mission of exploration. He is seen off on his first mission as commander of the starship by his father George Kirk, his brother Sam, and his family. (TOS: "What Are Little Girls Made Of?", "The Menagerie, Part I"; Star Trek; VOY: "Q2")
- A vintage of Dom Pérignon is made. A bottle from this year's vintage will be used in the christening of the USS Enterprise-B in 2293. (Star Trek Generations)
- The Enterprise becomes one of the first Earth ships to reach the edge of the Milky Way Galaxy, where they encounter the galactic barrier. Gary Mitchell and Elizabeth Dehner are among the Enterprise officers who die in the line of duty. (TOS: "Where No Man Has Gone Before")
- At a Christmas party held in the Enterprise science lab, Captain Kirk meets Dr. Helen Noel. She later recalls him "dropping in" on the party, during a mission to the rehabilitation colony on Tantalus V. (TOS: "Dagger of the Mind")
- Ingraham B is attacked by neural parasites. (TOS: "Operation -- Annihilate!")
- Carter Winston dies on the planet Vendor. (TAS: "The Survivor")
- The Borg "swarm through" the El-Aurian system, invading and destroying the El-Aurian homeworld. The survivors flee and are scattered over the entire galaxy, with some reaching Earth 28 years later. (TNG: "Q Who", Star Trek Generations)
- A new uniform is introduced for Starfleet personnel, though the previous style continues to be used for years. These new uniforms remain in service until the early 2270s. (TOS: "Dagger of the Mind", "Friday's Child"; TAS: "The Counter-Clock Incident"; Star Trek: The Motion Picture)
- Captain Christopher Pike is promoted to the rank of fleet captain. (TOS: "The Menagerie, Part I")
- April Wade is born. (DS9: "Prophet Motive")
- Nancy Crater is killed by planet M-113's last surviving native. (TOS: "The Man Trap")
- The pilot episode "Where No Man Has Gone Before", produced in 1965, is the only production set in this year.
- According to the script for "The Wrath of Khan", David Marcus was born in this year. However, in the script for "The Search for Spock", David was described as being in his mid-twenties.
- According to the Star Trek: Star Charts (p. 52), an Earth colony was founded on Cestus III.