In 2003 Evelyn Salt (Angelia Jolie) is tortured by North Korean soldiers who accuse her of espionage. She is soon traded for a North Korean prisoner and escorted to safety by her boss Ted Winter (Liev Schreiber). While walking towards the border, she asks why she was set free, and it is explained that her boyfriend Mike (seen staring at her from the other side of the border) was petitioning everyone in the government for her to be set free. Thus, in order for them to stop him from stirring up more unneeded publicity, they agreed to make an exchange.
In the present day, Salt is watching her now husband Mike working at the breakfast table with spiders (he is an arachnologist, meaning he studies spiders for a living). After he notices her standing there, he says happy anniversary. She offers to cook him breakfast, but he passes, mocking her cooking. The scene then cuts to her at work, learning online how to fold a napkin into a certain pattern so that the anniversary dinner she has planned is perfect. Winter interrupts, they chat for a while and then get ready to head out as its close to the end of the workday. As they are leaving, another agent chases them and finally tells them that a defector has come in and wishes to give them information. Wanting to see if the Russian has any useful information, Salt and Winter head back upstairs. Neural scans are set up in order to determine if the defector is lying, and Salt enters the room and begins the interview.
The defector begins by saying that his name is Orlov and proceeds by telling her a story about a Russian espionage program set up during the Cold War in which children of American families were kidnapped then replaced with Russian children that had been trained to be sleeper cell spies by a Russian official in hopes of restoring Russia's dominance one day. These agents are called K-12s and are supposedly a myth. They would assume the child's identity until Day X, the undisclosed date of action in which they would strike. Day X is apparently coming, and its events will apparently begin with the murder of the Russian President at the U.S. Vice President's funeral the next day in Manhattan and will finish with the U.S. President's assassination a day later.
Winter tells her to wrap up the interview, as they do not believe him. As she is leaving, he explains that the agent that will murder the President is Evelyn Salt. Salt leaves the room and is visibly upset. As she walks into the viewing room where her colleagues are, it is determined by the neural scan that he was being truthful throughout the interview. She begins speaking to the Counter Intelligence officer named Peabody and Winter, claiming her innocence. Winter is believing her and begins speaking to Peabody about how to proceed. Orlov is escorted out by two agents and goes into an elevator with them. Salt is given her phone in order to contact Mike as, when the cover of an agent is blown, often their whole fake life is in danger. She is told to wait in the interrogation room while they attempt to figure out how to proceed. As she watches Winter and Peabody argue, she realizes that she is in danger.
Cut to Orlov in the elevator. A blade comes out of his shoe, and he proceeds to kill both guards with him and escape. Winters and Peabody are alerted to Orlov's escape, giving Salt the opportunity to escape the room and attempt to get out of the building. As the security of the building begins to tighten, she finds herself cornered in the interrogation room again where she rigs up an explosive device to fire at the SWAT team. She fires it, knocking them unconscious and is able to steal a gun in the process. She then uses the gun to break a window and proceeds to climb onto the roof then onto the street. She gets into a taxi, attempts to call Mike again and hangs up after again getting their apartment's voicemail. She breaks her SIM card and then gets out of the taxi cab at her apartment building. As she walks in, she notices Mike's chair has been knocked over and how his sandwich is half eaten. There has obviously been a struggle, and he has been kidnapped.
As Salt packs her bag and takes some of Mike's spiders, Winters and Peabody are assembling a SWAT team to go to her apartment to see if she is there. They arrive just as she is climbing out of her window. She narrowly escapes and climbs into a neighbor's apartment. As she speaks to the child in the apartment and changes her clothes, she flashes back again to her husband and parts of their lives together. She escapes and while walking away from the building, is spotted by Winter. Another chase ensues, and Salt is cornered when she then jumps onto a semi truck passing under the overpass that she is on. The agents follow her and shoot as she jumps from one truck to another then finally lands on the ground. She then steals a motorcycle and manages to outmanoeuvre them and escape.
At this point, Salt heads to a bar. While in the bathroom, she steals the coat and ID of a fellow patron, takes a bus to New York City. Upon arrival, Salt uses the stolen ID to rent a small hotel room. There, she dyes her hair and steals clothes. She then begins to plan out how to get into the cathedral and prints a subway map.
At this point, another flashback shows us that Evelyn Salt is indeed a Russian implant spy. She was born and grew up in Russia and was taken in at a young age with a group of other young boys to become sleeper spies as part of the K-12 group. They were tought to speak English at a young age as well as learn the society and ways, customs and laws of the USA.
The next day, she boards a subway train and plants a smoke device. While everyone is distracted, she gets off the train and into the tunnels beneath the cathedral. As she gets into position in the crypt, the funeral begins taking place in the church. As the Russian President gets up to deliver a speech, Salt throws an explosive device onto the roof (which is directly under where the president is standing) and the floor crumbles below him, causing him to fall into the crypt beside her. Panic ensues and she presumably shoots the Russian president. Peabody comes in, and she surrenders despite having the opportunity to shoot him.
As she is taken away, Winter screams that he hopes she rots in jail for what she has done. She is put into an SUV and is transported in a caravan through the city. She then manages to eject both of her guards from the car and stun the driver, causing him to wreck the police cars ahead of and behind them. To escape, the other police now swarming around her, she drives the SUV over the guardrail and into the street below, wrecking the car. As the public come to see if everyone inside is all right, Salt escapes.
The news is, at this point, covering the death of the Russian President and the riots that are now happening across Moscow. Salt is then seen on a ferry boat and heads to a scrap metal yard. There, she meets with Orlov and embraces him. It is revealed that he is the man who took her in and trained her to become a Russian spy. She is then taken to a ship in the Hudson that serves as the Russian spies' home base. There, she is told that the next step of their plan is to seize nuclear weapons and begin a large-scale war between Russia and the USA to destroy the world. After being taken into the hull of the ship, she sees Mike being held hostage. To see whether or not she is loyal, Orlov shoots him dead and watches her reaction. When she fails to react, he introduces her to her fellow brother spies and then escorts her into his office to divulge more details about the plan. Once hearing that she is to meet with a spy disguised as a NATO officer the next morning and travel with him to Washington, DC, Salt pours them both a drink and then she suddenly smashes the wine bottle and rams it into Orlov's neck. Salt then uses a grenade to kill all of the Russian sleeper agents on the boat. Afterwords, Salt leaves the boat and goes to the rendezvous point to meet with her contact NATO officer.
After he arrives and boards the plane, she recognizes him as one of her fellow classmates and flashes back to more of her spy training as a child in the former USSR. They talk about their lives and their childhood. It is revealed that Salt was the best in her class and how she will finish first in this plan as well. He reveals that the plan will be to kill the US President while he is in his security bunker at the White House. Upon their arrival in Washington, he gives her a new ID and is disguised as a fellow NATO officer. After getting into the White House, he reveals that he is going to sacrifice himself by threatening the President by blowing himself up as a suicide bomber so that he will flee to the bunker where Salt is to kill him. Winter is among the group of men around the President and fleeing with him to the bunker. As they all get into the elevator to head down to the bunker, Salt is above them, jumping from floor to floor in the elevator shaft framework. Once on the bunker's level, she proceeds to disable the guards outside and pass safely into the bunker before the door is securely closed.
In the bunker, the President is raising the terror alert in the country to Def-CON 2 as Russia is apparently deploying their nuclear weapons in retaliation for what they see as an act of war (the killing of their President by a CIA agent). After the level is raised and the president is given full authority to launch the US missiles, Winter sees Salt approaching on CCTV and demands that the agents arm themselves. Suddenly, he grabs a gun kills all those in the room. Finally, it is just him and the President. (In this out-of-the-blue twist, Ted Winter is another Russian spy just like Evelyn Salt.)
After telling the President to activate strategic nuclear deployment strategies and being denied, he hits the President and knocks him unconscious. Salt has witnessed all of this. She approaches the bulletproof window and beckons Winter to use the President's hand to reauthorize and activate the strategic strike on Mecca and Tehran. She begins speaking to him through the glass, appealing to him by asking why he never told her that he too was a spy. She begs him to let her join him and finally he relents. As Winter is turning to go to the door to let her in, the news flashes on the television, saying that the Russian President is not dead as previously thought and had merely been given a paralytic. Realizing that Salt used venom from Mike's spiders so that it appeared that she had killed him, Winter says that he didn't trust her after she came back from North Korea. He knew from the start that she had fallen for Mike and was not the same person that she had been. That was why Ted Winter told Orlov to kidnap and kill Mike, as well as why she was being made into the patsy and why Winter would be seen as the hero. Salt is enraged at this point and attempts to fire her gun through the glass. When this fails, she sees the access box next to the door on the other side of the room. She goes to it on the other side, firing her gun at it until the wall behind it is exposed. She then rewires the box so that she can get into the bunker conference room.
In the room, Salt and Winters fight. The activation of the weapons is almost complete, but at the last minute, the secret service arrives and overpowers them. Instead of giving herself up, Salt jumps to pull the plug on the computer, cancelling the weapon strike activation and is shot in the process. Both she and Winter are escorted out, and as she is wearing a vest, Salt is unharmed. As she is being led up from the bunker as a prisoner, she sees Winter getting his wounds treated next to the stairs. She jumps toward him, wrapping her handcuffs around his neck and jumping over the balcony to strangle him. By the time she is pulled up, he is dead after neck has been broken and she is handed over to Peabody.
They board a helicopter, and he asks her why she killed Winter. Her reply is "someone had to". She then explains her side of the story, and Peabody begins to believe her but points out that no one else will. She says that there are more Russian sleeper spies out there that will stop at nothing to interfere. She convinces him to let her go as they have taken everything from her and she will stop at nothing until all of the spies of K-12 are dead. He then undoes her cuffs and she jumps from the chopper, escaping into the Potomac River.
(Director's Cut) As she reaches land and is running away, a news report voice-over states that the new President, Stevens paused to lay flowers for a plane crash in 1974 killing his parents and sister, while in a tour of Russia.