When a crewman from a landing party investigating the latest planet visited by the Enterprise returns under some form of exterior control and then dies, Kirk decides to beam down and see for himself what caused the death. What Kirk, Spock and McCoy find on the surface is a house of horrors right out of ancient Earth mythology, right down to three hideous witches delivering a prophecy of doom for the crew. Two aliens are found to be at the heart of the evil activities, and they have no intention of letting Kirk or the Enterprise leave their world.
Taking Federation Commissioner Hedford back to the Enterprise's sick bay so McCoy can treat her for a potentially dangerous but curable ailment, the shuttlecraft containing Kirk, Spock, McCoy and Hedford is diverted by a strange energy field to a barren planet, inhabited only by Cochrane, who invented the basis for current warp engine technology decades ago and should be dead by now. Cochrane reveals, however, that an energy creature called the Companion has halted his aging process. The Companion is also concerned about Cochrane's psychological well-being, and Kirk and the others have been brought to keep Cochrane company - possibly for the rest of their lives.
The Enterprise rushes to an underdeveloped planet in an attempt to stop Klingon intervention in the somewhat primitive society. The Klingon Krag is trying to convince the planet's people that an alliance with the Klingon Empire would be beneficial, and when Kirk breaks cultural taboos - not to mention the prime directive - by interfering with a routine killing and saving a pregnant woman, it becomes all too easy for Krag to point out that the landing party from the Enterprise have only come to usurp the planet's ways of life.
The Enterprise is trapped in deep space by an enormous hand. Kirk and a landing party beam down to a nearby planet and find that a powerful being claiming to be the Greek god Apollo is the one responsible for holding the Enterprise in its place - and Kirk discovers that Apollo's ability to immobilize a starship is just a small demonstration of the being's power. When Apollo demands that the crew worship him, Kirk decides that the mythical figure must be defeated - but must rely on playing with Apollo's emotions and weaknesses since the being can tamper with the Enterprise's technology.
Spock begins acting strange - even violent - as, unknown to the rest of the crew, he enters the Vulcan mating phase that strikes adult male Vulcans every seven years. Kirk must divert the Enterprise from a tight schedule to return Spock to Vulcan so his mating ritual may be carried out. But on arriving, it is discovered that Spock must compete with a gladiator of his prospective mate's choice - and that turns out, on the spur of the moment, to be Kirk.
The starship Constellation is found in deep space, almost completely destroyed. The only person found aboard is Commodore Matt Decker, in a state of shock and only able to give minimal details of what happened. A gigantic ship/creature suddenly returns, well over ten times the size of the Federation vessels, capable of literally eating entire planets to replenish is colossal energy needs. Kirk is trapped on the unarmed Constellation, while Decker takes command of the Enterprise and plans to exact revenge on the huge alien vessel, no matter what the risk to Kirk's ship and crew.
After suffering a head injury on the Enterprise, Scotty is talking into shore leave with Kirk and McCoy. On the planet they are visiting, however, a series of grisly murders of local women begins, and all the evidence seems to point to Scotty. Kirk must contend with the overwhelming evidence against Scotty as well as the overzealous local constable, who is ready to have Scotty punished as soon as possible.
The Enterprise is attacked and boarded by the unusual space probe Nomad, which Spock identifies as the combined remains of an alien robot and an Earth exploration probe. Nomad's purpose - a confused mix of aliens' orders and instructions from Earth - is to seek out and sterilize all impurities, including imperfect beings like humans. The only thing preventing Nomad from obliterating the Enterprise and everyone on board is the similarity between the name of Nomad's creator and Captain Kirk, and Kirk must try to play that role as best he can while figuring out how to get rid of Nomad.
An Enterprise landing party beams down to an edenic planet, where Kirk discovers that the people living there are still primitive, all progress held in check by an enormous ancient computer known as Vaal, which also demands sacrifices of food by the natives. Vaal detects the Enterprise in orbit and begins to drain it of its power, and Kirk realizes that he will have to destroy Vaal to save the Enterprise, but the surface dwellers' lifestyles will be changed forever if Vaal is removed.
Returning to the Enterprise from an unsuccessful mission to ask the leaders of a planet for a possible mineral trade, Kirk, Uhura, Scotty and McCoy are being beamed up just as a freak accident hurls them into another reality, which still contains a USS Enterprise and a Spock and a Federation, but the other reality's versions are cruel and inhumane - the crew the alternate Enterprise is readying for a strike against the planet Kirk just left to take their mineral resources by force. Kirk and his landing party must try to cover their inexplicable identities and try to fit in, while stopping the savage alternate Enterprise from carrying its reign of terror any further.
Conducting a survey of a planet, a landing party from the Enterprise is contaminated with a form of radiation sickness that accelerates aging. With the ship's entire command crew rapidly aging and slowly losing their ability to perform their routine duties, Commodore Stocker, who is aboard for a trip to his next starbase command, decides he must question their competency and take the captain's chair as Kirk, Spock and the others face an impending death of old age.
The Enterprise is taken over by Crewman Norman, who turns out to be an android in disguise. He sets the ship on a course back to his home world, a planet populated entirely by androids - and one Harry Mudd, trapped there after a crash-landing. The androids plan to move out beyond their own planet to populate the galaxy with more of their logical, efficient kind, and the Enterprise is their chosen means of transport. Kirk, although understandably suspicious of Harry, must now cooperate with the con-man if the android invasion is to be stopped. And the greatest weapon at the disposal of Kirk, his crew, and Harry is total illogic.
The Enterprise is summoned to space station K-7 for security duty when the station's security forces are considered inadequate to guard a shipment of valuable grain by the standards of Federation agriculture administrator Baris. A shipload of Klingons stops off at the station as well, which has all parties concerned even more about the grain consignment. Kirk orders stepped-up security, but that only results in some of the crew - including Scotty and Chekov - instigating a massive bar brawl with the Klingons. All the while, the seemingly harmless huckster Cyrano Jones is trying to peddle furry tribbles off to anyone with a few credits, and Uhura buys one and takes it back to the Enterprise, not knowing that tribbles do only two things: eat and breed. William Campbell returns in the Deep Space Nine story "Blood Oath" to wreak further havoc - sans Tribbles.
Trying to track down the crew of the downed Federation starship Beagle, Kirk, Spock and McCoy arrive on a planet populated by a society that mixes savage ancient practices with 20th century technology. Enemies of the Roman Empire-like state are rounded up and forced to participate in televised coliseum battles. Kirk and Spock briefly encounter a peaceful group of people, but all are captured and prepared for their duels - including one event which will pit Spock against McCoy. Kirk must hope that he and his landing party can survive long enough for help to arrive from the Enterprise.
Delegates from several worlds are welcomed aboard for a trip to Babel where a Federation summit will take place, among them Vulcan Ambassador Sarek - Spock's father, from whom he has been alienated since childhood. Spock's human mother, Amanda, can't stop trying to bridge the gap between her husband and son, while Spock and Sarek can't seem to do anything but continue their rivalry. When a hidden assassin begins to kill some of the delegates, Spock - out of logic, of course - points Sarek out as a potential suspect. But Sarek suffers a heart attack just as an alien ship begins to attack the Enterprise. Kirk is stabbed by the assassin, and Spock must choose between offering some of his blood to save Sarek's life and assuming command of the Enterprise in the emergency.
The Enterprise visits a primitive world where the Klingon Empire has armed one faction of people against another in hopes of eliminating the weaker population and allying the stronger warriors with the Klingons. Spock is seriously injured when he, Kirk and McCoy beam down, and is returned to the Enterprise for treatment as Kirk and McCoy try to make contact with the locals. Kirk is injured by an poisonous indigenous animal, but reaches, with McCoy's help, his old friend Tyree. Tyree's mystical wife Nona cures Kirk and then pursues him. Kirk and McCoy, in the meantime, may only be able to resolve the unfair advantage between the planet's two factions by arming Tyree against his people's Klingon-backed adversaries.
A landing party beaming down to the Enterprise's latest stop is intercepted by a more powerful, long-range transporter beam, which hijacks Kirk, Uhura and Chekov to the planet Triskelion, where they are immediately handed over to various "trainers" to prepare them for their upcoming duties as gladiators to amuse the powerful rulers of the planet. Spock orders the Enterprise to warp to Triskelion to save the landing party but doesn't realize that the powers-that-be on the planet may want to lure the Enterprise crew there to provide them with even more entertainment.
While a landing party is conducting a routine survey of a planet, two crewman are killed and one badly injured by a cloudlike being Kirk suddenly believes he has encountered before. It turns out that the creature attacked a ship that Kirk had been stationed on years before and killed most of the crew, and Kirk feels that he should have been able to do more to save his former crewmates. He transfers that guilt to the surviving landing party member, who not only is considered responsible by Kirk, but is also the son of Kirk's former captain on that previous assignment. Kirk orders the Enterprise to follow the creature through space, determined to kill it - at any cost - before it can take more lives.
Spock telepathically receives the collective death cries of the entire all-Vulcan crew of the USS Intrepid, which has just been destroyed by an unknown force. The Enterprise intercepts a gigantic organism, which then surrounds the ship, beginning to cause physical and mental illness among the crew. Kirk, Spock and McCoy surmise that this paradoxically huge single-celled organism may be a "disease," as its course will soon take it through inhabited star systems. The Enterprise may turn out to be the only "antibody" capable of saving millions from the onslaught of the enormous parasite.
The Enterprise encounters a planet recently visited by another starship and discovers that a book on the Chicago mobs of the 1920s accidentally left behind by a crew member of the previous ship has become the basis of the planet's society structure over 200 years of the planet's time (the starship having had warp drive). The intelligent but imitative inhabitants show a keen interest in replacing telephones with communicators and replacing tommy guns with phasers when Kirk, Spock and McCoy - along with their standard Starfleet landing party equipment - are captured.
The Enterprise responds to a distress call, finding only a trap set by a small group of aliens from the Andromeda galaxy who are assessing the potential of the Federation's home galaxy for colonization. The aliens successfully take over the ship, reducing all aboard except for Kirk, Spock, McCoy and Scotty to dehydrated cubes so the ship's supply of food and oxygen can be used by the hijackers and Kirk's command crew for the staggering 300-year return to Andromeda. The aliens, having assumed human form, also gain attributes such as emotions, which may be just the weakness Kirk and the others need to attack to regain control of the Enterprise.
The Enterprise visits a planet long thought uninhabited, and finds globes that contain the consciousness of the last survivors of the planet, Sargon, Thalassa and Henoch. The three remaining beings wish to "possess" the bodies of willing Enterprise crew members, leaving the crew members' minds in the globes briefly as Sargon and his companions use the human bodies to construct android bodies for their minds. Kirk, Spock, and Dr. Mulhall agree to this procedure, but Henoch, occupying Spock's body, has other plans than building an android frame for himself. In the meantime, Sargon and Thalassa, in the bodies of Kirk and Mulhall, fall in love all over again. One way or another, though, the humans' bodies must be vacated since their metabolism is incapable of withstanding the levels of activity taken on by Sargon and the others.
On arrival at Ekos, the Enterprise is the target of a nuclear missile attack, a technology which didn't exist the last time a Federation ship visited the planet. Kirk and Spock beam down to investigate, discovering that the government on Ekos has been transformed into a Nazi police state which came about when Federation teacher John Gill tried to simply increase the efficiency of the government on Ekos. Gill is now under the control of the people he has tried to educate, and anyone who tries to reveal the truth about Gill or rescue him - including Kirk and Spock - are hunted men.
Kirk is ordered to relinquish command of the Enterprise to Dr. Daystrom's new M-5 computer, which, according to Daystrom, can make all the decisions that a starship captain would encounter correctly and more quickly than any human. The Enterprise, with Kirk and a few others aboard, is engaged in Starfleet wargames, but the M-5 begins to treat the other ships as a serious threat and retaliates with full salvos of phasers and photon torpedoes, destroying one ship. Believing Kirk may have lost his mind, Starfleet gives the remaining ships permission to destroy the Enterprise.
The missing starship Exeter is spotted in orbit of an inhabited planet. Kirk, Spock and McCoy board the Exeter, finding only the remains of the crew, wiped out by a disease which likely affects the boarding party now. Transporting to the planet, Kirk finds that Captain Tracey of the Exeter escaped his crew's fate, and the atmosphere on the planet is capable of eliminating the disease from the Enterprise landing party's bloodstreams. But more problems arise as Tracey discards his loyalty to the prime directive in an attempt to gain power in the planet's government.
After warping back in time to the late 20th century for a glimpse of Earth's past, the Enterprise intercepts a mysterious man who simply calls himself Gary Seven. Although Gary and his ever-present black cat Isis appear like inhabitants of the 20th century, Gary knows what kind of ship he is on and recognizes Spock as a Vulcan, and ascertains that the Enterprise is from the 23rd century. Gary Seven evades security officers and resumes his journey to Earth. Kirk and Spock assume 20th century disguises and pursue him, finding that Gary is a time traveler from the future who is here to influence Earth's history - but whether or not his influence will be benign is another question altogether.