Major Bennett Marco, Sergeant Raymond Shaw, and the rest of their infantry platoon are captured by an elite Soviet commando unit during the Korean War in 1952.

Years after the war, Marco, now back in the United States working as an intelligence officer, begins suffering a recurring nightmare in which the seated platoon members are surrounded by a group of sweet little old ladies who had been a part of their brainwashing.

It is revealed that the Communists have been using Shaw as a sleeper agent who, activated by a post-hypnotic trigger, immediately forgets the assignments he carries out and therefore can never betray the operation either purposely or inadvertently.

Married to McCarthy-esque Senator Johnny Iselin, Eleanor has convinced the Communist powers to help install her husband as president and allow them to control the American government through him.

"[3] Jonathan Lethem, in his influential essay "The Ecstasy of Influence: A Plagiarism", included Condon's novels as "texts that become troubling to their admirers after the discovery of their 'plagiarized' elements".

The 1962 adaptation, considered a classic of the political thriller genre, was directed by John Frankenheimer, and starred Laurence Harvey as Shaw, Frank Sinatra as Marco, and Angela Lansbury as Eleanor in an Academy Award-nominated performance.

The film updated the conflict and setting the Persian Gulf War in 1991, had a U.S. corporation (called "Manchurian Global") as the perpetrator of the brainwashing and conspiracy instead of foreign Communist groups, and dropped the Johnny Iselin character in favor of making both Shaw and his mother elected politicians.

The head of the project grants Shaw a "gift"; after his brainwashing, he becomes quite sexually active, in contrast to his reserved nature beforehand where he had not even kissed his love interest, Jocelyn Jordan.

Rosie, Marco's love interest, is the ex-fiancée of one of his associates handling the Shaw case for Army Intelligence, making things between the couple tense.

The 1962 version does not state outright the political affiliation of Senators Iselin and Jordan (implied to be Republicans), although in the 2004 film the equivalent characters are Democrats.

In the 2016 MCU movie, "Captain America: Civil War," Tony Stark references the novel, nicknaming the Winter Soldier, Bucky Barnes, "Manchurian Candidate".