Evelyn Salt interrogates a Russian defector, Orlov, who tells her about “Day X”, an operation organized by a powerful Russian since the Cold War, which will lead to the destruction of the United States. Orlov mentions that at the funeral of the late Vice President in New York City, the visiting Russian President will be killed by Russian spy Evelyn Salt. Salt, shaken at the accusation, attempts to contact her husband Mike, a German arachnologist, fearing for his safety. Meanwhile, Orlov escapes, prompting Salt to escape causing the CIA to think she is a spy. She flees to her apartment and finds her husband missing. Salt resumes and grabs essentials as well as a venomous spider. After barely escaping a highway pursuit, Salt takes a bus to New York City. The next morning, she sneaks into the heavily guarded St. Bartholomew’s Church where the Vice President’s funeral is being held and shoots the Russian President. She then encounters Peabody where she surrenders but escapes the NYPD.
A series of flashbacks show Salt growing up in the Soviet Union where Orlov taught her and many other children to obey him and ingratiate themselves to the American government. Then, when it came to Day X, he would command them to strike from various positions in the US. Salt meets Orlov who congratulates her on her killing. He brings her to a river barge, where he tests her allegiance by having another agent kill Mike in front of her. Salt appears to be unaffected by this, thus passing Orlov’s test. He then tells her Part Two of Day X, which would involve seizing the United States’ stock of nuclear weapons. Salt, who had gone to Orlov only to discover his plans, kills Orlov and everyone else on the barge. She then goes to the rendezvous set up by Orlov to meet a NATO mole.
The NATO mole and a disguised Salt go to the White House. Once inside, her NATO counterpart suddenly starts shooting at Secret Service agents and detonates a bomb. The Secret Service, along with Winter, rush the President to the lower bunker of the White House. Meanwhile, the President, believing Russia is preparing a nuclear strike against the US, begins to transmit the launch codes from the nuclear football. Salt infiltrates the bunker and kills the bodyguards. Winter picks up a gun and kills everyone but the President, whom he knocks unconscious.
He explains to an astonished Salt that he was part of Orlov’s plan all along. Winter then uses the nuclear football to start the sequence for launching nuclear missiles at Tehran and Mecca. Salt asks Winter to let her in but before he opens the door, a news program reveals that the Russian President is not dead, but only placed in a near-death state from spider venom. He realizes that Salt is not on his side but she manages to break in, and after an intense struggle, she succeeds in knocking him down. Just after she manages to abort the nuclear missile launch set up by Winter, agents break in and arrest her. Winter goes free, but later Salt uses her chains to strangle him.
Salt is put on a helicopter with Peabody, and explains everything to him. A skeptical Peabody finally accepts she is telling the truth after he receives an SMS saying that her fingerprints were found at the barge, confirming her betrayal to Orlov. They both know that there are other moles, and Peabody agrees to let her escape, so she can find and kill them. He uncuffs her and Salt jumps into the river, free once more.