It's been more than 10 years since Army Major Ben Marco (DENZEL WASHINGTON) and his men fought in the Gulf War, but he's still troubled by a singular but repeating nightmare and vision -- featuring Dr. Atticus Noyle (SIMON MCBURNEY) -- that's led him to believe that something mysterious happened to his unit in Kuwait. When that suspicion is confirmed by Al Melvin (JEFFREY WRIGHT), another deeply troubled vet, Ben sets out to learn whether what they all seem to remember being true -- namely that fellow soldier Raymond Shaw (LIEV SCHREIBER) took command, saved their lives and become a war hero -- really is.
He wants to meet Raymond, but unlike the major, Shaw is an up and coming political star. His mother, U.S. Senator Eleanor Prentiss Shaw (MERYL STREEP) has persuaded her party to have him, rather than senior Senator Thomas Jordan (JON VOIGHT), selected as the Vice-Presidential running mate for candidate Robert Arthur (TOM STECHSCHULTE). Raymond and Jordan go back a ways as Shaw once dated Jordan's daughter, Jocelyn (VERA FARMIGA), but the domineering Eleanor put an end to that.
After a brief meeting with Shaw gets him nowhere, Ben suspicions grow as he believes there was a conspiracy to brainwash him and his men into thinking that Shaw's actions in Kuwait happened, when they really didn't. Of course, no one believes Ben and those protecting Raymond become increasingly worried that the major may become a liability, especially when the candidate is meeting with executives from defense contractor Manchurian Global.
On his way to seek help from underground researcher Richard Delp (BRUNO GANZ) who may be able to answer his questions about mind control, Ben runs into grocery clerk Rosie (KIMBERLY ELISE) who takes an unusual interest in Ben and his predicament. With time racing toward the election and Raymond possibly becoming the next Vice-President, Ben worries that something greater than just a fabricated memory is at play and sets out to discover what that is.