While investigating a distress call from Talos IV, Captain Christopher Pike of the starship Enterprise is captured and tested by Talosians, beings who can project powerfully realistic illusions.

After the Enterprise attempts to cross the Great Barrier at the edge of the galaxy, crew members Gary Mitchell and Elizabeth Dehner develop "godlike" psychic powers which threaten the safety of the crew.

The Enterprise visits planet 113 for a routine medical inspection of the husband-wife archaeological team stationed there, but find that the wife has been replaced by a deadly, shape-shifting creature.

While traveling aboard the Enterprise, a dangerous young man named Charlie Evans terrorizes the crew with his unusual mental powers

After the Enterprise attempts to cross the Great Barrier at the edge of the galaxy, crew members Gary Mitchell and Elizabeth Dehner develop "godlike" psychic powers which threaten the safety of the crew.

A strange, intoxicating infection, which lowers the crew's emotional inhibitions, spreads throughout the Enterprise. A crew member's inebriated actions place the ship in danger, forcing Scotty to perform a hazardous and untested engineering procedure to save the ship from destruction.

While beaming up from planet Alpha 177, a transporter accident splits Captain Kirk into two beings: one "good," who acts weak and indecisive; and one "evil", who acts overly aggressive and domineering. Scotty must quickly repair the transporter system to reunite the two Kirks, and to rescue the landing party trapped on the surface of the icy planet below.

The Enterprise encounters interstellar con man Harry Mudd, who is arrested on outstanding charges while ferrying three extraordinarily beautiful women to a remote planet, destined to be wives for the miners located there. In actuality, the plain-looking women use illegal Venus drugs, which make them appear to be much more attractive than their natural appearance; after the drugs wear off, revealing Mudd's deception.

In search of Nurse Chapel's fianc, renowned exobiologist Roger Korby, the Enterprise visits the icy planet Exo III, where Korby has discovered an ancient machine which allows him to duplicate any living person with an android replacement. Korby plans to use the machine to spread controlled androids throughout the Federation, and replaces Captain Kirk with such a duplicate in an effort to take over the Enterprise.

After discovering what appears to be a duplicate of the planet Earth, Captain Kirk and his landing party find a population ravaged by a strange disease, which only children appear to have survived.

While on a re-supply mission to a rehabilitation colony for the criminally insane, the Enterprise crew discover that the inmates have taken over the asylum and kidnapped Kirk and his companion. Spock performs a mind-meld for the first time in this episode.

The Enterprise is menaced by a gigantic alien ship whose commander condemns the crew to death. The alien ship appears all-powerful and the alien commander refuses all attempts at negotiation, forcing Kirk to employ an unorthodox strategy to save the ship.

Spock hijacks the Enterprise to take his crippled former captain, Christopher Pike, to the forbidden world of Talos IV. He then demands a court martial where he uses the events of "The Cage" to tell the tale of Pike's captivity on the planet years earlier.

Spock continues detailing the events of "The Cage" to the tribunal. After witnessing the Talosians' capabilities of mental illusion, Kirk realizes that Spock intends to return Pike to the planet to live a life of illusion, unencumbered by his crippled condition.

While visiting an old friend, Kirk learns of suspicions that a Shakespearean actor may actually be the murderous former governor of the planet where Kirk grew up. Kirk invites the acting troupe aboard the Enterprise in order to investigate. But soon, assassination attempts are made on Kirk and another crewman who was an eyewitness to the murders.

While investigating a series of destroyed outposts, the Enterprise discovers a lone Romulan vessel with a cloaking device. The Romulans, having never been seen by humans, are revealed to visually resemble Vulcans, casting doubt on Mr. Spock's loyalty as the two ships become locked in a cat-and-mouse battle through space.

Captain Kirk orders shore leave for the Enterprise crew on a seemily unihabited planet in the Omicron Delta system. The landing parties begin to see strange sights, such as the White Rabbit, Don Juan, and a sword-wielding samurai. Kirk sees (and fights) an image of Finnegan, a rival from his Starfleet Academy days. Spock discovers that the planet seems to be drawing a large amount of energy from the ship's engines, placing the Enterprise in danger.

Spock and a scientific party are sent to study the Murasaki 312 quasar aboard the shuttle Galileo. During the survey, the Galileo is forced to make an emergency landing on the planet Taurus II, where the crew fight the planet's dangerous inhabitants. As the crew begin to make repairs, Scotty determines that the shuttle does not have enough fuel to reach orbit carrying all seven passengers, and Spock must contemplate leaving some of his fellow crew behind.

The Enterprise discovers a rogue planet drifting through space, inhabited by an eccentric being named Trelane who uses his apparently unlimited power over matter and form to manipulate the crew.

The Enterprise comes under attack by unknown aliens while investigating the near-destruction of the Cestus III colony. While chasing the aliens into unexplored space, both ships are captured by the powerful Metrons, who force Kirk and the alien captain (later identified as a member of the Gorn race) to trial by combat: the winner's vessel will be set free, while the loser's ship will be destroyed.

After accidentally traveling back in time to 1969, the Enterprise rescues USAF Captain John Christopher from his crippled fighter jet. The crew struggles to return to their own time, while simultaneously returning Christopher to the Air Force, removing his knowledge of the future, and all record of contact with the Enterprise.

Captain Kirk is placed on trial for negligence after a crewman is killed during a severe ion storm. Kirk maintains that his actions were proper and should not have led to the officer's death, but the evidence is strongly against him. All seems lost until new evidence prompts Kirk's attorney to use an innovative defense strategy.

The Enterprise discovers a planetary population controlled by a powerful being called Landru. While investigating, Captain Kirk and his landing party are taken captive and discover that the Enterprise crew will be the next to be "absorbed" into Landru's control.

The Enterprise discovers an ancient sleeper ship, the SS Botany Bay, which escaped from Earth's Eugenics Wars in the late 20th century. The genetically engineered passengers, led by war criminal Khan Noonien Singh, seize control of the Enterprise and attempt to destroy the ship.

On Eminiar VII, the Enterprise finds a civilization at war with its planetary neighbor. Unable to discern any signs of battle from orbit, Captain Kirk leads a landing party to the surface where he discovers the entire war is fought by computer. Even though the war is simulated, citizens who are listed as virtual casualties still report to termination booths to be killed for real. After the Enterprise is destroyed in an attack simulation, Kirk must fight to keep his crew from death.

Despite exposure to deadly radiation, the Federation colony on Omicron Ceti III appears to be thriving. A landing party from the Enterprise investigates, finding the colony's population to be healthy beyond explanation. Leila Kalomi, an old friend of Mr. Spock, shows the landing party strange flowers that seem to impose a state of pure bliss on all exposed to its spores (even Spock). The spores effects spread rapidly throughout the Enterprise, causing the crew to mutiny against Captain Kirk.

Dispatched to the mining colony on Janus VI, the Enterprise is tasked to investigate rumors of a strange, subterranean creature responsible for destruction of equipment and the deaths of fifty miners. Kirk and Spock discover a silicon-based life form, a Horta, which lives in the surrounding rock. After wounding the creature, Spock performs a mind meld, discovering the reason behind the Horta's attacks.

Peace negotiations have collapsed between the Federation and the warlike Klingon Empire. The Enterprise is ordered to protect Organia, a peaceful planet located near the Klingon border. Kirk and Spock beam to the surface to warn the Organians about the Klingons, but soon a Klingon fleet arrives, forcing the Enterprise to abandon the duo on the planet. The natives protect Kirk and Spock, even as Kor, the new Klingon governor, orders mass executions of the Organian people. As both Federation and Klingon fleets converge above the planet, Kirk and Spock execute a daring raid on the Klingon headquarters in an effort to destabilize their control over the planet.

While orbiting an apparently dead planet, the Enterprise seems to experience a strange moment of "nonexistence." Captain Kirk discovers a man named Lazarus on the planet below, who claims the effect was caused by his "enemy," later revealed to be an insane version of Lazarus from an alternate dimension. The sane version of Lazarus asks for Kirk's help in defeating his counterpart.

After accidentally overdosing on a powerful stimulant, Dr. McCoy acts erratically and disappears through the Guardian of Forever, a newly-discovered time portal on a remote planet. Kirk and Spock follow after learning that McCoy somehow changed history. Arriving in the 1930s, the duo meet Edith Keeler, a New York social worker who gives them a place to stay. As the days pass, and McCoy is nowhere to be seen, Kirk finds himself falling in love with Keeler... but Spock discovers that Keeler must die to restore the timeline.

The Enterprise arrives at Deneva - the home of Captain Kirk's brother, Sam - and discovers that the entire planet has been infested with large, amoeba-like aliens that have attacked and killed much of the human population. One of these aliens attaches itself to Spock, who volunteers to become a subject in Dr. McCoy's medical tests. After McCoy accidentally blinds Spock during one of his test procedures, the doctor must quickly find a way to neutralize the dangerous creatures.