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Kirk is relieved of command after having violated the Prime Directive to save Spock's life. Soon after, a secret Starfleet weapons's research facility is blown up by a mysterious captain Harrison. The latter then attacks the building where all high-ranking Starfleet officers are gathered to discuss the first attack. Harrison transports to a uninhabited area of Kronos, the Klingon homeworld, and Kirk is sent there to blow him up with a set of top-secret, advanced photon torpedoes. Kirk then decides to catch Harrison instead of simply blowing up the whole area. Harrison reveals that his is actually Khan, a bioengineered super-human created 300 years ago and revived in secret by admiral Marcus to develop weapons. The latter belives that the war with the Klingon is unavoidable and that Starfleet must become an armed force. Khan also reveals that he had hidden in the torpedoes the bodies of 72 other super-humans that he tried to protect from Marcus, who was using them as hostages to force Khan to work for him. Soon after leaving Kronos, Enterprise is attacked by a mysterious Starfleet ship, heavily armed, and commanded by Marcus. The latter wants Khan and the super-humans back. After boarding the ship with Kirk, Khan takes control and sends Kirk back to Enterprise in exchange for the torpedoes. Enterprise escapes towards Earth, chased by Khan who has discovered that the torpedoes are empty but armed, and disable the ship. Khan then crashe onto Starfleet's headquarter, while Kirk, in an attempt to prevent Enterprise to do the same, dies from radiation poisoning repairing the engine. Spock then chases Khan (who had survived the crash) to take a sample of his blood, ther latter having regenerative properties, and saves Kirk's life. Some time later, Kirk and Enterprise leave for a five year exploration mission.

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Spock's half-brother Sybok, who decided to follow his feelings rather than logic, has kidnapped a Terran, Romulan and Klingon embassadors on a planet in the Neutral Zone in order to attract a Federation starship (the new, unfinished Enterprise) and take it over. He manages to convince the crew and especially its captain, Kirk, to take him to the center of the galaxy, inside the Great Barrier to a planet believed to be the craddle of all life in the galaxy, and where God might be living. The entity they meet is rather evil and not a god at all, and the heroes eventually manage to escape the planet after Sybok was is killed by the entity, thanks to the help of a Klingon Bird of Prey which was following the Enterprise in an personal attempt by its captain to gain honor by defeating Kirk.

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Kirk's father encounters a Romulan ship coming out of a black hole and dies throwing his own ship at the enemy to protect the crew's escape, among who is his wife and newborn son, thus changing history. Kirk's youth is tumultuous, but finally joins the Starfleet Academy and cheats at the final exam (a computer simulation where one cannot win, programmed by Spock, a Starfleet officer half Vulcan, half Human, who has always had a hard time controlling his emotions). But during the hearing for cheating, all the officers are ordered to leave to Vulca without delay to help with a natural catastrophe. Kirk manages to sneak into the Enterprise thanks to his friend, the Dr. McCoy, and manages to convice the captain that they are throwing themselves at warp speed into a trap laid by the same Romulan ship his father faced in the past. The Romulan captain, Nero, coerces the captain of the Enterprise into joining him, while Kirk (promoted first officer), Sulu and ensign Expendable are sent to deactivate the device that jams communications and transporter (a giant drill, drilling a hole into Vulca). Their mission is a success, but Nero nonetheless manages to send Red Matter into the hole, which turns into a black hole and absorbs the whole planet. Spock's mother dies despite Spock's attempt to save her. Disagreements between him (acting captain) and Kirk about the course to take (regroup with the Federation ships or chase Nero heading to Earth) prompt him to strand Kirk on an ice planet near a Federation outpost. On the planet, Kirk meets Spock from 129 years in the future, who tells him that he tried to save Romulus from a supernova, using Red Matter in order to absorb the star, but failed. Both the Romulan ship and Spock's go back in time through the ensuing black/wormhole, but arrives 25 years earlier than Spock. Nero picks Spock up when he appears on the other end of the wormhole and holds him responsible for the destruction of Romulus and condemns him to watch his own planet being destroyed. Spock and Kirk reach the outpost where they find an “exiled” Scott trying to build a long-distance transporter. Thanks to Spock's knowledge, Scott and Kirk transport aboard Enterprise. Kirk forces Spock to punch him, forcing him to resign his his comission. Kirk, acting captain, chases Nero, and with the help of Spock manage to prevent Nero from destroying Earth. Young Spock finally meets Old Spock, who tells him that they need each other, because this his how it had been in the original reality.