Prior to an important conference at U.N.C.L.E. headquarters, a bizarre series of events occurs revolving around a strange man Mr. Hemmingway (Richard Haydn) who keeps appearing and disappearing at will in the building. Solo and Illya learn that he has been placed there by Waverly to test the security system, but THRUSH also has an inside agent, Riley (Peter Haskell), who plants an exploding false tabletop on the conference table at the direction of Dr. Egret (Lee Meriwether). Solo has only a few minutes, before the conference is to begin, to try and find out who the infiltrator is.

Solo and Illya agree to help Major Morgan (Gene Raymond), Solo's old commanding officer, steal a national symbol sceptre for his people from a dictator. Morgan is killed and Solo and Illya and Zia (Ziva Rodann), Morgan's female aide, are captured and sentenced to death. After they escape, they find that Morgan is still alive and has duped them into stealing the sceptre for him because of the precious gems it contains.

Waverly's cousin is killed by his own dog when he refuses to sell his stock to a gypsy named Delgrovia (Paul Lambert), so Illya investigates and, with the help of Ursula (Susan Oliver) and dog expert Guido Panzini (Pat Harrington Jr.), traces two of the dogs to Delgrovia's estate, where he and Ursula are soon cornered by a pack of deadly Doberman pinschers.

Solo and Illya protect a young Himalayan prince (Michel Petit) and his nurse (Susan Seaforth) from THRUSH agents who want to kidnap him one of whom turns out to be his bodyguard.

Solo uses the former girlfriend (Kathryn Hays) of 2 brothers, Joseph and Max Van Schreetan (Gerald Mohr, Lloyd Bochner), to thwart their plan to control the diamond market, while at the same time THRUSH agent Corio (Alfred Ryder) tries to steal their cache of gems.

Waverly is poisoned, and taken to a hospital where he is subjected to the rays of a brain-altering machine by THRUSH agent Dr, Dabree (Elsa Lanchester) designed to make him ineffective without killing him. While investigating others who have suffered the same fate, Solo finds Cecille Bergstrom (Yvonne Craig) and together they try to unravel the mystery and save Waverly.

Solo is aided by tourist Bernie Oren (Glenn Corbett) in finding a black market auction in Hong Kong run by Mr. Cleveland (Gavin McLeod) that sells military secrets, including a microfilm in a rare coin. Oren is infatuated with Heavenly Cortello (Karen Sharpe), and hinders more than he helps Solo, while Illya tries to infiltrate the auction disguised as a Mongolian warlord.

U.N.C.L.E. Portuguese translator Mandy Stevenson (Barbara Feldon) hungers for more excitement, so Solo sends her on a fake mission to get Waverly's tobacco not realizing she has taken an important microfilm that THRUSH is after. Solo, Illya and THRUSH pursue her through the streets of Manhattan, and eventually she and Solo are captured by the THRUSH leader, Victor Gervais (Cesar Romero), and Solo has to use his skills as a marksman to escape.

Solo attends a revival meeting conducted by evangelist Brother Love (Eddie Albert), who is actually a THRUSH leader constructing a nuclear spaceship with the aid of a kidnapped scientist, Dr. Hradny (Robert H. Harris). College student Pearl Rolfe (Maggie Pierce) is kidnapped by Love's followers, and Solo must rescue both victims and destroy Love's plan at the same time.

Squire G. Emory Partridge (George Sanders) kidnaps Illya and lures Solo to his manor in order to kill them off in his dungeon torture chamber in revenge for a past encounter. But Peggy Durance (Bonnie Franklin) helps them escape, with the unintended aid of Partridge's bumbling wife Edith (Jeanette Nolan).

Solo and Illya travel to the Riveria, where they search for a serum that supposedly provides great strength and even brings the dead back to life. There they meet Madame Streigau (Marian Moses), who is actually Dr. Egret of THRUSH, as well as Lucia Nazarone (Danica d'Hondt) and her bevy of beautiful blonde helpers. With the help of teacher Lavina Brown (Kipp Hamilton), they trick Mazarone into thinking they have the serum also, and become the targets of her "superwomen".

Retired U.N.C.L.E. agent Albert Sully (Martin Balsam) is brought back to impersonate a crime syndicate leader, and insists on leaving Solo and Illya behind and running the operation himself. He reunites with wartime fellow agent and old flame Bryn Watson (Barbara Shelly) and tracks down a secret crime conference, with the exasperated Solo and Illya trying to keep him from being killed in the process.

Alexander a megalomaniac industrialist, plans to conquer the world like his namesake, Alexander the Great by breaking each of the ten commandments along the way. he has his henchman Parvix steal the army's ""will gas"" to help him do so, and Solo investigates. Solo encounters Tracey Alexander, Alexander's ex-wife, who wants to tag along with Solo to get the money Alexander owes her. The trail leads Solo, Illya, and Tracey to a posh party at Alexander's, where Solo defeats him in a human chess game; to a tomb, where Alexander and his aide Dr. Kavon leave Solo tied under a descending scimitar while Illya and Tracey are hanging over a bottomless pit with a candle burning their rope; To Alexander's farm in Virginia, where Illya is nearly cut in two by various farm implements.

Alexander a megalomaniac industrialist, plans to conquer the world like his namesake, Alexander the Great by breaking each of the ten commandments along the way. he has his henchman Parvix steal the army's ""will gas"" to help him do so, and Solo investigates. Solo encounters Tracey Alexander, Alexander's ex-wife, who wants to tag along with Solo to get the money Alexander owes her. The trail leads Solo, Illya, and Tracey to a posh party at Alexander's, where Solo defeats him in a human chess game; to a tomb, where Alexander and his aide Dr. Kavon leave Solo tied under a descending scimitar while Illya and Tracey are hanging over a bottomless pit with a candle burning their rope; To Alexander's farm in Virginia, where Illya is nearly cut in two by various farm implements.

Illya Kuryakin infiltrates a South American prison camp where Thrush are storing the 'Ultimate Computer'.

U.N.C.L.E. and Thrush agents compete to gain possession of a mind-reading device created by a magician who has been murdered by Thrush.

Napoleon Solo is given the job of searching for Thrush security records.

The 'Re-collectors' claim to be trying to locate works of art stolen by the Nazi's but all is not as it appears.

Illya goes to find Thrush's vaporizing machine, but is captured by Sophie, the headstrong daughter of the local tribal chief, Sulador. in New York Solo convinces retiring THRUSH agent David Lewin that THRUSH intends to kill him, and elicits his help. Lewin and Solo are taken to the base in the desert, just as Illya leads the band of nomads, whose confidence he has gained, in an attack on the base.

Solo and Illya go to India to help Suzanne de Serre, a French botanist trying to find out why the jungle is dying and local natives are disappearing. Prince Panat and Drusilla Davina, along with Colonel Quillon, are systematically using a chemical to destroy the jungle and kidnapping natives to work in the jewel mines for the prince.

THRUSH is so eager to get their hands on a boy genius that they murder the boy's father. But then they have to deal with the boy's madcap aunt.

THRUSH eastern in Japan acquires a volcano-activating device, and Solo and Illya, along with Cricket Okasada, a film student, infiltrate a toy store and a karate school to find it. THRUSH leader Mr. Kutuzov oversees local THRUSH head Harada in the operation, and Solo finds himself fighting for his life against a life size sword wielding puppet.

French fanatic Robespierre seeks to destroy France's vineyards in his quest for virtue, and Solo enlists the aid of scientist Raoul Dubois and his daughter Albert in combating the plan. Illya is captured by THRUSH agent Carl Voegler and, with a target painted on his back, is hunted through the woods by Voegler's archers.

A top-level U.N.C.L.E. conference is to be held in Switzerland, but a nearby boys' school is actually a THRUSH front run by Mother Fear and Dennis Jenks that is training its students to be assassins. Solo is captured by the boys, and, when he refuses to reveal the conference location, is forced to operate the controls of two electric trains so they do not collide with each carrying a vial of deadly nerve gas. Illya and Anna Paola, a social worker who resent children, are also captured. The escape, and arrive at the conference just as the boy's choir is ready to kill Waverly and the others with THRUSH rifles from under their robes.

Solo and Illya board the Adriatic Express train on New Year's Eve to intercept Madame Nemirovitch, a THRUSH agent who is carrying a chemical that is capable of stopping the reproductive process. Eva, a young girl who delivers a message to Madame Nemirovitch as the train leaves, is caught on board. Throughout the evening, the THRUSH agent and Solo and Illya engage in a battle of wits as the train speeds along its route.