Visiting Berlin headquarters in preparation for a high level U.N.C.L.E. conference, ""Summit Five,"" Solo finds agent Heinz Newman (Don Chastin) mysteriously murdered. Illya goes to Berlin, as does Harry Beldon (Albert Dekker), one of Waverly's counterparts in Section 1. Beldon suspects that either Solo or Gerald Struthers (Lloyd Bochner) committed the murder, while Illya suspects Beldon's secretary Helga Deniken (Suzanne Cramer), but Beldon himself turns out to be the traitor, and he plans to kill Waverly at the conference.

A dying UNCLE agent warns Napoleon and Illya that a group of supermen is being bred by THRUSH. The duo discover a school set up by the enemy organization in Mexico, who has already produced 7 emotionless killer students! As a graduating exercise, one is chosen to eliminate Solo and Kuryakin after they follow the boy to Austria.

Solo and Illya are asked by Adam Tenza (Chad Everett) to protect his millionaire industrialist father Mark Tenza (Broderick Crawford) from assassination by THRUSH, much to the resentment of the elder Tenza. When Tenza is killed by a bomb, Solo and Illya must find out where J Tenza's other son, James is, to protect him also. But Adam Tenza is actually planning to kill J, in order to hand his father's empire over to THRUSH.

Solo and Illya are assigned to investigate a mysterious ray from the sky that killed the inhabitants of an African village. They find expert safecracker and fugitive from justice Luther Sebastian (Bradford Dillman), now a leader of a cult called the Third Way, and enlist his help in their plan to break into to the safe of Parviz Kharmusi (John Dehner) and steal the thermal prism that powers that deadly ray. Solo runs into Annie Justin (Carol Lynley), who is looking for Sebastian, who framed her boyfriend. Azalea (Lola Albright) helps Solo escape from Annie, and takes him to Kharmusi. But Sebastian reveals he has stolen the prism for himself so he can put it into orbit and extort the world.

Solo and Illya are assigned to investigate a mysterious ray from the sky that killed the inhabitants of an African village. They find expert safecracker and fugitive from justice Luther Sebastian (Bradford Dillman), now a leader of a cult called the Third Way, and enlist his help in their plan to break into to the safe of Parviz Kharmusi (John Dehner) and steal the thermal prism that powers that deadly ray. Solo runs into Annie Justin (Carol Lynley), who is looking for Sebastian, who framed her boyfriend. Azalea (Lola Albright) helps Solo escape from Annie, and takes him to Kharmusi. But Sebastian reveals he has stolen the prism for himself so he can put it into orbit and extort the world.

In Portugal, Solo is taken prisoner by Pharos Mandor (Jack Lord), a THRUSH chief ready to defect if his arch rival, THRUSH assassin Stepan Valandros (Nehemiah Persoff), does not kill him first. Solo meets Mandor's girlfriend, Cathy Welling (Leslie Parrish). Mandor tells Solo U.N.C.L.E. must kill Valandros or he will not defect, but his real aim is to eliminate Valandros and promote himself up the THRUSH ranks.

THRUSH agent Barnaby Partridge (Michael Rennie) uses his island gambling casino to brainwash VIP's into committing suicide by playing on their secret fears. U.N.C.L.E. sends Taggart Coleman (Charles Drake) to the island to help Solo and Illya uncover the process, and he encounters an old love interest there, Monica (Nobu McCarthy). But Partridge takes Illya prisoner and subjects him to the process training him to kill Solo.

Illya recuperating in the hospital, is kidnapped by an old enemy, Viktor Karmak (Darrin McGavin), to lure Solo into a trap. Solo follows a clue to a twelve block condemned area of Manhattan, and finds modern artist Sheila Van Tillson (Marlyn Mason). Karmak appears and announces that Solo has until dawn to find Illya before a deadly gas kills him, while Karmak and his pet jaguar will try to hunt Solo down at the same time.

In a Latin American country, Illya and Solo try to help the popular national leader, Angela (Madlyn Rhue) protect her government from the Secret Three, a revolutionary group backed by THRUSH. Solo is captured by the Secret Three, but escapes after learning that Vinay (Victor Ludlin), a friend of Angela's is plotting against her. He tells her husband, General Abaca (Joe Sirola), but the general is actually the one plotting to overthrow his wife's government and have her killed.

Illya goes to U.N.C.L.E.'s secret island training academy, the Survival School, to help Jules Cutter (Richard Beymer) find a THRUSH infiltrator who has assassinated a trainee. Suspicion focuses on three trainees Melisa Hargrove (Susan Odin), John Saimes (Chris Robinson), and Harry Williams (Charles McGraw), and Illya must find out who is the real double agent.

Solo and Illya go to visit a Nazi war criminal in prison, Von Etske (Will Kulova), but find that he has escaped with the aid of a special thought controlling device. His escape was observed by photographer Terry Cook (Judy Carne). Von Erske is joining forces with Zorgon Gurnius (George Macready), a fellow former Nazi, to reactivate their wartime triumvirate. Illya intercept Nexor, and finds that he is his exact double. He decides to impersonate Nexor to foil the plan.

Solo and agent Andreas Petros (Robert Wolders) are sent to the island of Ibos, where the Technological Hierarchy for the Removal of Undesirables and the Subjugation of Humanity has been spending huge amounts of money on some unknown project. Solo, posing as a visiting THRUSH official, meets Dr. Killman (John Larch), the head of the project, and Marnya (Barbara Luna), who reveals that Killman is working on an earthquake device, as the real THRUSH emissary arrives.

Oliver Barnes (Lawrence Mantaigne), a THRUSH agent, unsuccessfully tries to destroy a package. Solo and Illya suspect a connection between this and a new ""molecutronic gun"" developed by Dr. Fabray (William Marshall). Solo runs into Abbe Nelton (Anna Capri). Fabray turns out to be a THRUSH collaborator. The entire scheme was a plan to get Illya to take the ""gun"" actually a bomb, into U.N.C.L.E. headquarters in Trojan Horse fashion.

In London U.N.C.L.E. agent Brian Morton (Peter Bromilow) is planning on getting married much to Waverly's disapproval. Solo and Illya help Morton on his current mission, stopping THRUSH agent Commader Kroler (Alfred Ryder) from stealing the plans for a new supersubmarine. Waverly tries to dissuade Laura Adams (Diana Van Der Vlis), Morton's fiancee, but to no avail. Morton and Laura are then kidnapped by Kroler, and Kroler threatens to kill Laura if Morton does not obtain the sub for him.

Mr. Webb (Mark Richman), a THRUSH agent, and Margitta Kingsley (Eleanor Parker), the wife of U.N.C.L.E. agent Robert Kingsley (Barry Sullivan), plot to steal a docility gas from General Maximilian Harmon (Leslie Nielson), who has kidnapped Professor David Garrow (Dan O'Herlihy) and his son Steve (Tony Bill). Harmon and a group of scientists consider themselves the ""Seven Intellectual Wonders of the World"" and, with the gas and the troops, plan to take over control of the world and ensure peace.

Mr. Webb (Mark Richman), a THRUSH agent, and Margitta Kingsley (Eleanor Parker), the wife of U.N.C.L.E. agent Robert Kingsley (Barry Sullivan), plot to steal a docility gas from General Maximilian Harmon (Leslie Nielson), who has kidnapped Professor David Garrow (Dan O'Herlihy) and his son Steve (Tony Bill). Harmon and a group of scientists consider themselves the ""Seven Intellectual Wonders of the World"" and, with the gas and the troops, plan to take over control of the world and ensure peace.

In Africa, Professor Kenton has developed a superman formula which he has been using on the natives, hoping to build an army with which to conquer all of Africa. Premier Khufu resists the use of the drug on his people. Illya meets up with Harry Blackburn, a shady safari guide, and Marsha Woodhugh, who is searching for her lost sister, a Tarzan like woman named ""Girl"" who has captured Solo.

A dying man carrying a partial film with the secret of Project Quasimodo, a miniature atomic bomb, gives only one clue to finding the rest of the film: the name of Marvin Klump, inept car salesman. THRUSH agents Rodney Backstreet and Beirut capture Klump. Solo and Illya, with the aid of Klump's sister Heather, follow them first to the Alps, them back to the U.S.,where the answer to the puzzle lies in a cemetery.

Illya goes to the Himalayan country of Chupat to protect the high lama, but is shot by ""Calamity"" Rogers, an American rodeo star. Solo is sent to find Illya, and learns that the prime minister has kidnapped the real successor to the throne and intends to install his own son instead. An entranced girl, Amra Palli tries to kill Solo after being brainwashed by the prime minister.

Solo and Illya must protect Premier Georgi Koz, a Khrushchev like European leader, on a visit to New York, Priscilla Worth is befriended by Loz and she takes him to a school for Santa Clauses run by Francis X. O'Reilly where just one of a series of assassination attempts against him must be thwarted by the two U.N.C.L.E. agents.

In Greece, Illya tries to recover stolen U.N.C.L.E. documents, but they fall into the hands of Stavros, a Greek bandit, who has ambushed Illya, thinking he is his daughter Kira's convict husband, Manolakas returning from prison. Kita is in love with Nico instead, and Solo and Illya must resolve the love triangle in order to retrieve the documents.

THRUSH agent L.C. Carson uses an Indian reservation as a front for his plan to assemble a hydrogen bomb, and kidnaps the tribe's chief, High Cloud, to ensure cooperation. Solo arranges for the Chief's daughter Charisma to return, but she ends up being kidnapped along with Solo and Illya, who is disguised as an Indian. Solo and Illya, along with a band of young Indian warriors on Motorcycles, encircle Carson and his men and try to stop them before its too late.

President Nasasos Tunik visits Paris. His assistant, Malanez, is determined to persuade the president that the French are his enemy, and arranges for various embarrassing and insulting incidents to occur. Solo and Illya are assigned to see that the visit goes smoothly, but Tunik falls in love with Candyce, and Malanez plans to disgrace Tunik by framing him in a plot to steal the body of Napoleon from his tomb.

Solo and Illya find that THRUSH agent Colonel Picks has developed exploding apples, which will be used to trigger a nuclear stockpile. Nina Lillette, a pretty hillbilly girl, latches onto them for excitement. Illya joins a picking crew at the farm, but he is buried alive in a tunnel with the volatile apples.

Solo and Illya visit the laboratory of Dr. True, who has discovered how to extract gold from seawater. But Dr. True dies from a poison given him by THRUSH agent Randolph, and Randolph also kills his wife Amanda. The gold extraction formula was distributed in portions by True to his daughters, in inscriptions on a photo of himself. Solo and Illya meet Sandy True, who accompanies them to Rome, to find her half sister Margo, now unhappily married to the destitute Baron de Fanzini to London, to find the next sister Imogen, who has been arrested by a Constablefor indecent exposure and finally the Alps, to find Yvonne, who is breaking off an unhappy relationship with Karl Von Kesser. But after decoding the message in Japan, Solo, Illya and Sandy are captured by Randolph and taken to THRUSH central for execution.