In Berlin, an UNCLE employee is killed just as he is sending a message to Waverly about a security breach. This occurs just before UNCLE's Summit Five conference, when the leaders of UNCLE's five regions meet and new communications codes are activated. Solo is a suspect in the killing and is subjected to an intense interrogation. Solo and Kuryakin must find the real traitor before it's too late.
Thrush is using a fencing school in Mexico as a cover. Inside, young men are being trained to be "perfect" killers. They can even turn emotion on and off. Professor Stoller, the head of the operation, has selected his prize pupil, Greg Martin, to demonstrate how effective the trainees can be. Martin is to blow up a dam in Greece and destroy a small town in the process. Solo and Kuryakin desperately try to stop the young Thrushman. Complicating matters is a young woman who has fallen in love with Martin.
Dr. Kharmusi, a criminal scientist, has developed a "thermal prism," which generates intense heat beams. UNCLE recruits Luther Sebastian, wanted for various crimes in 22 countries, because he designed the kind of safe where Kharmusi keeps the prism. Napoleon Solo infiltrates Kharmusi's base of operations as an amoral businessman while Illya Kuryakin and Sebastian work to steal the device. However, Annie, whose boyfriend was framed for murder by Sebastian, complicates matters.
Solo, Kuryakin and Annie narrowly escape a deathtrap set by Luther Sebastian, whose Third Way cult now has the "thermal prism" developed by the late Dr. Kharmusi. Sebastian next intends to hijack a U.S. rocket so he can launch the prism into orbit and blackmail the world.
Mandor, a former high-ranking Thrush official, supposedly has defected to UNCLE. In reality, he is providing information that will weaken his enemies within Thrush; Mandor is angling to take over Thrush in a power play. However, a former Mandor associate is hunting him. Mandor arranges it so that Illya Kuryakin is captured, forcing UNCLE to kill the Thrushman hunting Mandor. Napoleon Solo must rescue Kuryakin and then deal with Mandor.
Barnaby Partridge, an ambitious Thrush operative, runs a casino in the Carribean, where he brainwashes prominent visitors. Solo recruits a businessman who's still in love with a woman in Partridge's employ. Kuryakin, meanwhile, is captured while infiltrating the casino. The Russian agent is programmed to kill Solo.
Karmak, given up for dead by Napoleon Solo and Illya Kuryakin, kidnaps Kuryakin to extract his revenge on Solo. Solo must find Kuryakin, who is somewhere in a 10-block area of condemned buildings, before 6 a.m. or else the Russian UNCLE agent will die.
Kuryakin foils an assassination attempt on Angela Abaca, an Evita Peron-like leader of a South American country. Authorities initially jail him, mistakenly believing he's part of the plot. Instead, he's hailed as a hero, which now impedes his ability to protect Angela. Solo is sent to the country and masquerades as a mercenary. Solo learns that Thrush has collaborators inside the government. Meanwhile, Angela makes it difficult for Kuryakin to protect her.
Kuryakin is sent to UNCLE's secret training school on a remote island. He has to find out which trainee among of a soon-to-graduate group is really a mole for Thrush. Helping him is another agent posing as a trainee. Kuryakin must also deal with the obsessive head of the school, Jules Cutter.
A Nazi scientist is sprung from a German prison, with Solo and Kuryakin in pursuit. While the scientist escapes, one of the plotters is killed. Kuryakin impersonates the man and travels to South America. Solo goes to the continent separately, but cannot shake a woman photographer who had been on the scene when the scientist escaped. It turns out Thrush is financing the plot, which involves a mind-control ray, which is to be used on Washington just as the president is scheduled to speak before Congress.
UNCLE sends Solo and Petros, another agent, to Irbos, an island near Greece. They discover that Dr. Killman, a Thrush scientist, has enslaved the island's population to build a new destructive device. Filene, a Thrush official who has just arrived on the island, is accidentally killed during a fight. Solo takes his place, the basis of the episode title. Meanwhile, Petros is captured. Thrush is impatient and is ready to end Dr. Killman's project, complicating Solo's situation.
Thrush, after an unsuccessful attempt to blow up UNCLE's New York headquarters, decides on a more elaborate scheme. The title refers to how Thrush's new plan takes various twists and turns. If Solo and Kuryakin don't figure out the puzzle, UNCLE headquarters will be demolished.
Thrush covets a new nuclear submarine, which will be launched from England. The criminal organization also employs the woman who is engaged to marry Brian Morton, UNCLE's top enforcement agent in Europe. Waverly joins Solo and Kuryakin in England and takes a direct role in the affair.
Robert Kingsley, a top UNCLE official who is based in Hong Kong, mysterious disappears. He is recruiting top people in various fields. He wants to end "the never-ending battle" between good and evil "in favor of good." His method: a "docility" gas. Napoleon Solo and Illya Kuryakin are sent to find Kingsley. What Kingsley doesn't realize is his wife is allied with Thrush, which is financing his dream.
In the series finale, Napoleon Solo and Illya Kuryakin must oppose both former UNCLE official Robert Kingsley's forces as well as Thrush. Solo, in a strongly worded talk to Kingsley's "Seven Wonders of the World," spells out why Kingsley's dream is a nightmare. Unable to convince them, he and Kuryakin face a firing squad.