The film starts on the Class M planet Nibiru. Captain James T. Kirk (Chris Pine) is running through a red forest from the planet's inhabitants. He runs into a beast and stuns it. Dr. Leonard "Bones" McCoy (Karl Urban) chastises him because that was their ride. They continue running and contact Mr. Spock (Zachary Quinto), who is in a shuttle with Mr. Sulu (John Cho) and Lieutenant Uhura (Zoe Saldana). Spock is set to detonate a cold fusion device into a volcano to prevent it from destroying the planet. He is lowered into the volcano but his line burns off and he falls onto a rock. Meanwhile, Kirk and Bones jump off a cliff into the ocean where the Starship Enterprise is waiting for them. They try to reach Spock, who is still in the volcano. In an attempt to get him out, Kirk breaks the Prime Directive and has the ship rise from the ocean, exposing them to the inhabitants but successfully beaming Spock out, just as the device detonates and crystallizes the volcano's magma.
In London, a couple, the Harewoods, go to the Royal Children's Hospital to visit their ailing daughter. It appears that things are not looking well for her. The father, Thomas (Noel Clarke), steps outside and is approached by a stranger, John Harrison (Benedict Cumberbatch), who tells him that he can save his daughter.
At the Starfleet Headquarters in San Francisco, Kirk and Spock meet with Admiral Pike (Bruce Greenwood). He knows Kirk risked the crew's life after exposing the Enterprise to the Nibiru inhabitants after Spock filed a report. After taking it up with Admiral Marcus, Pike tells Kirk that he is no longer in command of the Enterprise, and he is being sent back to the academy, as Pike is now re-assuming his position as captain.
Harrison gives the Harewoods' daughter a transfusion of his blood, which proves successful. Afterwards, Thomas, seen in a Starfleet uniform, goes to the London headquarters. He sends a transmission to Admiral Marcus and drops a ring into a cup of water, dissolving it and causing it to explode and blow up the facility.
Kirk goes to a bar to drink away his sorrows when Pike shows up. He tells Kirk that Spock is now transferred to the USS Bradbury, and, after talking to Admiral Marcus, he has decided to allow Kirk to become Pike's new first officer, as he believes Kirk deserves a second chance. Pike then receives an emergency message.
On his way to meet with Pike, Kirk runs into Spock. He's still mad at him and tells him he saved him because he would have missed him. Spock doesn't reply, leaving Kirk to sigh and walk off. They meet with the other captains and first officers before Admiral Marcus (Peter Weller), who informs them that Thomas sent him the transmission stating that he was forced by Harrison to blow up the data archives at the facility. Kirk inquires about Harrison's motives, and then notes that the protocol for an event requires the captains and first officers to meet. At that moment, a red light flashes behind them, and a ship commandeered by Harrison begins to open fire. Kirk tries to hit it back and notices the ship's turbines. In the ensuing chaos, Pike is shot. Kirk ties his gun to a hose and tosses it at the turbine, which sucks up the hose and pulls it off the wall and into the turbines. He succeeds in taking the ship down, but Harrison beams out in time. Spock sits by Pike's side as he dies.
A while later, Spock tells Kirk that Scotty (Simon Pegg) found something in Harrison's ship with coordinates that lead to Kronos, a Klingon homeworld. Kirk and Spock know that Starfleet cannot go to Kronos directly, as it would possibly provoke war with the Klingons. With Marcus's approval, Kirk is given the order to take Harrison down.
Kirk, Spock, and Bones take a shuttle to the Enterprise along with new weapons officer Carol Wallace (Alice Eve). Once there, Scotty complains that the torpedoes given to the crew to fire upon Harrison could risk the lives of everybody on board. He resigns, along with his companion Keenser (Deep Roy). Kirk then assigns Chekhov (Anton Yelchin) to Chief Engineer. He then issues a message to Harrison, letting him know that he is prepared to fire the torpedoes upon him. Sulu takes the ship out at warp speed.
On their voyage to Kronos, Spock confronts Carol, telling her he knows she came under a false identity. Her last name is Marcus and she is the admiral's daughter. Suddenly, the warp core malfunctions. Kirk takes Spock and Uhura on a shuttle with two other Starfleet officers into Kronos. On their way down, Kirk learns that Uhura is still upset with Spock over his seemingly indifferent attitude during his moment in the volcano, and his inability to feel anything. Spock says he looked at Pike as he was dying and saw anger, confusion, and loneliness, and he does not know why he can't feel such emotions.
The trio is detected by a Klingon patrol ship, which chases them through the area until they are faced by other ships. Knowing that they would lose if they attack first, Uhura goes out to talk to them, as she speaks some Klingon. She tells the Klingon leader to help her find Harrison, as they would care about honor. Regardless, the Klingon attempts to kill her, but Harrison opens fire upon the Klingons. When they fight back, Kirk and Spock rush out to help Uhura. Harrison manages to kill all of the Klingons and confronts the trio. He asks how many torpedoes are on the ship, and Kirk tells him there are 72. Harrison appears surprised and surrenders. Out of retribution for Pike, Kirk begins hitting Harrison repeatedly, but he never fights back or reacts.
Harrison is now a prisoner on the Enterprise. Bones takes a sample of his blood, and Harrison asks why the ship hasn't continued moving. He inquires about the ship's warp core and offers to help Kirk, but Spock and Bones are obviously hesitant. Harrison gives Kirk the coordinates of 220.127.116.11 and tells him to examine the torpedoes.
Kirk calls Scotty, who is getting drunk at a nightclub with Keenser. Kirk gives him the coordinates and then has Carol and Bones go outside the ship and open a torpedo. It nearly goes wrong when Bones's hand gets caught in the torpedo as it almost detonates, and he can't be beamed onto the ship without the torpedo, but Carol successfully deactivates it. They are surprised to find that inside the torpedo is a man in cryo sleep.
Kirk confronts Harrison about the man in the torpedo. Harrison reveals that all the torpedoes contain members of his crew from nearly 300 years earlier. His civilization was unsuccessful in their voyages and were put into cryo sleep. It is also revealed that his name is not John Harrison, but it is, in fact...KHAN! He tells Kirk that he alone was awakened by Marcus because of his superior intellect to develop advanced weapons to go to war with the Klingons. He starts to break down with concern for his colleagues, appealing to Kirk's own devotion to his crew.
Scotty arrives at the destination of his given coordinates, where he finds a Starfleet shipyard. He happens upon something and is amazed by what he sees.
The Enterprise heads out, but is faced by an enormous ship that is nearly three times the size of the Enterprise, the USS Vengeance. Admiral Marcus reveals himself as the commander of the ship and orders Kirk to hand Khan over to them. Kirk tells Marcus that he is sending Khan to Earth to stand trial for his crimes. As they head into warp drive, the Vengeance manages to catch up to them and fires upon the Enterprise, killing several crew members. Kirk and Carol try to appeal to Marcus, as Kirk offers to hand Khan and his 72 colleagues to the Vengeance while Carol believes her father wouldn't destroy the ship with her on it. He beams Carol onto his ship and orders his crew members to continue firing upon the Enterprise, but their phasers shut down. Turns out Scotty has successfully disabled the weapons on the Vengeance.
The Enterprise is unable to move, nor can it fire back at the Vengeance, so Kirk decides to launch himself and Khan onto the other ship, with Scotty ready to open the door for them. As they are launched out, they encounter debris, which hits Kirk's helmet and knocks out his display, making it impossible for him to reach the ship's entrance. Khan helps him make it, but Scotty is confronted by a crew member of the Vengeance and is unable to respond. At the last second, Scotty opens the door to allow Kirk and Khan in and sucking the crew member out. Meanwhile, Spock gets in contact with Spock Prime (Leonard Nimoy) and asks him if he encountered Khan. Spock Prime uneasily tells him that Khan is the most dangerous enemy he's encountered, and he defeated him at a great cost.
Kirk, Khan, and Scotty fight their way through other crew members on the Vengeance to get to the bridge. Kirk tells Scotty to stun Khan, as he still doesn't trust him. Once they make it to the bridge, Scotty stuns Khan, and Kirk tries to arrest Marcus. However, Khan gets back up and attacks Scotty, Carol, and Kirk. He gets to Marcus and crushes his skull with his bare hands. Khan patches through to the Enterprise to negotiate with Spock - he will beam Kirk back to his ship in exchange for his colleagues. The exchange is made, and as Kirk, Scotty, and Carol are beamed back, Khan declares "No ship should go down without her captain."
Khan begins to fire upon the Enterprise, causing it to fall to Earth, but Spock reveals to him that the torpedoes were armed, and they detonate on the Vengeance. Khan screams as he believes his colleagues were killed, and the Vengeance starts to go down as well. It is revealed, however, that Bones got the colleagues out and left them on the Enterprise.
Kirk and Scotty rush through the falling ship to fix the warp core. They nearly fall to their deaths but are rescued by Chekhov. Kirk makes it to the warp core, but Scotty warns that they would die if they go in their due to the radiation. Kirk decides he has to do this alone, and he knocks Scotty out. He successfully kicks the warp core back into place, allowing the Enterprise to lift off once more. Scotty reawakens and calls Spock down, who finds Kirk weakened. Kirk tells Spock he is scared, and Spock begins to tear up. He acknowledges Kirk saved him on Nibiru because he considers him a friend. They give each other the Vulcan salute before Kirk finally dies. Angered, Spock yells "KHAAAAAAAAAAAAAAAN!"
The Vengeance falls to Earth and crashes into San Francisco, causing severe damage to the city. Chekhov gets a lock on Khan's location as he rushes out of the ship. They can't beam him up, so Spock is beamed down and chases Khan through the city. He catches up to him and they begin fighting. Meanwhile, Bones notices that a creature he transfused Khan's blood into has reawakened, and he realizes that he can use Khan's blood to revive Kirk. With no more blood, Bones tries to contact Spock and tells him he needs Khan alive. Uhura beams down to the shuttle on which they are fighting and she stuns Khan. Spock, still raging, whales on Khan, but Uhura stops him from killing Khan when she says he is needed to save Kirk. Spock delivers one final blow to knock Khan out cold.
Kirk awakens to Bones and Spock standing by him. He is thankful for them saving him. Khan, meanwhile, is put in cryo sleep along with his colleagues.
Sometime later, Kirk is at a re-christening of the Enterprise. He gives a speech honoring Pike and everybody else who lost their lives because of Khan. The crew plans on a five-year voyage of exploration, as Kirk states, "to boldly go where no one has gone before." Scotty has come back to his position, and Carol is now part of the crew as well. Kirk then declares "Take us out, Mr. Sulu", as Sulu takes them into warp drive once more.
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