In the pilot episode, UNCLE agent Napoleon Solo is assigned to foil an assassination plot by Thrush. The criminal organization's target is a delegation from the newly independent African nation, Western Natumba. The plot is under the supervision of Andrew Vulcan, a U.S. industrialist secretly working for Thrush. Solo recruits an old flame of Vulcan's as part of his plan.

Napoleon Solo travels to Iowa, the site of a secret U.S. Air Force base, after a saboteur turns up there. A group wants to hijack a secret U.S. plane as part of a plan to overthrow a South American nation.

UNCLE agents Napoleon Solo and Illya Kuraykin face a four-cornered conspiracy comprised of an ambitious woman (Gervaise Ravel), her wealthy boyfriend (Harold Bufferton), a disgraced military officer and a scientist who has devised a chemical that induces fear. Solo and Kuryakin are helped by the daughter (Marion Raven) of a man killed as a result of the conspiracy.

UNCLE agents Solo and Kuryakin are assigned to investigate hijackings at sea, where people are abducted from ships by a ship flying a pirate flag. The lead pirate, Captain Shark, believes the world will soon inevitably be destroyed by World War III and views his ship as a modern-day Noah's Ark.

U.N.C.L.E. and Thrush race to find a Nazi scientist, who worked for Adolf Hitler, after an SS officer assigned to guard the scientist turns up dead. The scientist, who now teaches under the name Professor Amadeus, has Hitler in suspended animation. He needs a person with the same blood type of Hitler's; the Nazi leader will need a completely new blood supply to come out of suspended animation. Amadeus discovers that Solo is the right blood type...

Solo investigates a Thrush plot to tamper with the minds of prominent people only to find out he has been expected all along. Now, Thrush intends to tamper with his brain, figuring the agent will eventually be promoted and be turned into a pawn of the criminal organization.

Solo and Kuryakin pursue Gervaise Ravel and Harold Bufferton, the surviving conspirators of The Quadripartite Affair. To draw them out of hiding, Solo will use Marion Raven as bait and utilize a variation of the Guioco Piano chess opening to make the operation a success.

Thrush seeks to control "Project Earthsave," an energy source to be used if Earth is ever invaded. Toward that end, the group has used plastic surgery to make one of its operatives into a double for Napoleon Solo. Solo is scheduled to lead a team of UNCLE agents who are acting as couriers with the new combination for the Project Earthsave vault.

A diplomat seeks to heighten tensions between East and West. UNCLE is to neutralize him but not, Waverly says, in a way he becomes a "cause celebre." Solo and Kuryakin devise a con game with a false secret (dubbed Project Strigas) and recruit a talented engineer who abruptly quit a lucrative job to start his own business.

Solo is trying to track down a chemical agent that hastens the aging process.

Solo seeks to find a group of scientists who are trying to start World War III. Chemicals that are destroying the Russian grain harvest are being launched by rockets off the West Coast of the United States.

Solo steals a dove-shaped medal from the body of the leader of a European nation as the corpse lies in state. The medal has information concerning Thrush personnel operating in the country. The UNCLE agent must contend with Satine, a master spy in the employ of the European nation as well as the country's security police, who are working for officials under the control of Thrush. Solo is assisted by Miss Taub, who is supervising a group of students on a European tour.

A deposed leader of a Middle Eastern nation, now living in Rome, is conspiring to ruin the economy of his country. Solo and Kuryakin adopt cover identities as part of a plan to foil the plot.

Solo and Kuryakin, spending some off-time in Rome, are approached by Clara, an old flame of Solo's. She seeks Solo's help so Emil, a gypsy leader, can escape Terbuf along with papers that implicate the corrupt leadership of that country. Kuryakin tags along. His knowledge of gypsies and clear head (where Clara is concerned) will be of great assistance to Solo.

Solo and Kuryakin are told to escort a captured Thrush official, Egon Stryker, to Washington. Meantime, Waverly transports a man the agents are told is a double for Stryker. A Thrush team keeps trying to whisk Stryker away.

Solo and Kuryakin plan to blow up a Thrush treasury containing $55 million. The facility's cover is a casino. The agents recruit a young Minneapolis woman and coerce an expert safe-cracker as part of their plan.

An UNCLE agent transporting a Thrush device is killed when members of a revived Thugee cult in India rob a plane and cause it to crash. Solo picks up the trail of the murdered agent. He must deal with both Thrush and the cult.

The mysterious Hemingway causes havoc at UNCLE headquarters in New York through various means, including tampering with the facility's water supply and electrical system. This occurs on the eve of an important conference where UNCLE will host leaders from around the world. Meanwhile, Thrush's Dr. Egret and Riley, a Thrush mole inside UNCLE, conspire to assassinate the leaders. Solo and Kuryakin try to figure out Hemingway's motives. Virtually the entire episode takes place at UNCLE headquarters.

Solo is on a personal mission to help Col. Morgan, who was Solo's commanding officer during the Korean War. Kuryakin accompanies Solo. The agents become involved in a conspiracy where all is not what it appears.

A relative of Waverly's is being threatened if he doesn't sell shares in a company at a fraction of their value. Kuryakin is assigned to the affair, where his knowledge of gypsies proves useful. Solo, recuperating from a knee injury, provides limited assistance.

Thrush seeks to assassinate the 10-year-old boy leader, who has brought peace to a formerly violent country.

A pair of cousins has robbed a diamond syndicate of a huge amount of diamonds. They are blackmailing the syndicate; if they're not paid, they'll flood the international market, devaluing diamonds everywhere. Both UNCLE and Thrush are seeking to find the diamonds.

Thrush poisons Waverly, with plans to subject him to a procedure that affects the brain. The criminal organization has already experimented on others, turning a shipping magnate and a diplomat into failures.

A single shilling is the object of a hunt between UNCLE and criminal groups in Hong Kong.

An UNCLE translator, Mandy Stevenson, seeks excitement. Solo, feeling sorry for her, "recruits" Mandy to be a courier. In reality, she is only supposed to get Waverly more pipe tobacco. Things go askew when Mandy is given actual valuable information (a list of Thrush agents in France). UNCLE and Thrush comb New York to find Mandy.

UNCLE investigates Brother Love, a religious figure, who uses his traveling revival to surreptitiously kidnap leading scientists for a new THRUSH operation.

G. Emory Partridge is seeking revenge on Solo and UNCLE for foiling a plot seven years earlier. Partridge kidnaps Kuryakin as part of a trap.

UNCLE and Thrush seek a formula that accelerates healing. The Thrush forces are led by Dr. Egret.

UNCLE, seeking to infiltrate a meeting of terrorists, reluctantly recruits former agent Albert Sully, a supposed expert on one of the attending terrorists. In reality, he knows no more than UNCLE does and, in turns, seeks the help of a woman from his past.