Investigating a sector of space where starships have disappeared every 27 years, the U.S.S. Enterprise male crew are attracted by a mysterious signal. Kirk beams down with a landing party and encounters a race of beautiful women who survive by drawing the energy from the male members of the ships that they have lured to their planet.
Patrolling near the Neutral Zone, the U.S.S. Enterprise finds a ship and rescues Carter Winston, a Federation citizen, financier, and philanthropist missing for 5 years. However, Winston turns out to really be a Vendorian, an alien species that can transform its shape at will. He is also allied with the Romulans.
On the recently-discovered planet Phylos, the U.S.S. Enterprise crew meets Dr. Keniclius, a human scientist who survived Earth's Eugenics Wars and now grown to giant proportions. The Phylosians are a once vast plant-based civilization that has been reduced to a few survivors. Led by Keniclius, the Phylosians abduct Spock so the doctor can make him into a giant clone with the intention of forcing peace on the galaxy.
The Enterprise travels to the center of the galaxy only to discover themselves sucked into a dimension where the laws of time and space no longer apply, and "magic" functions for those capable of grasping its fundamentals. Stopping at Megas-Tu, a planet where magic and witchcraft are the norm, the crew finds their guide is Lucien, who is Lucifer of Earth mythology.
Harry Fenton Mudd is once again apprehended and incarcerated by the U.S.S. Enterprise crew, after trying to sell love crystals. He claims the love potion can cause any male and female to fall in love. He inadvertently releases it into the Enterprise's ventilation system and they discover that his claims are true. Mudd abducts Nurse Chapel and briefly escapes to a rocky planet in a stolen Enterprise Heavy shuttlecraft, but he is recaptured and sentenced to an indefinite period in rehabilitation therapy for violations of the Federation pharmaceutical code, including fraud, illegal drug manufacturing, swindling, and transport of a dangerous life-form (a Rigellian hypnoid).
While exploring a burnt-out supernova, the U.S.S. Enterprise responds to an old-style distress signal containing the word "Terratin," and follow it to its source: an uninhabited planet about to shatter from internal stress. However, a mysterious beam strikes the ship and the crew begins to shrink... and shrink... On the planet, Kirk finds a miniature city called Terratin and soon discovers that it is a lost Earth colony that has mutated because of the supernova's radiation.
The U.S.S.Enterprise is sent on a mission to explore a "Bermuda Triangle of Space," only to find itself and a Klingon battlecruiser trapped in a time warp after being caught in an ion storm. The two ships must cooperate before their only exit back to real space closes for good. This Delta Triangle is inhabited by other lost ships, many centuries old.
Spock, Sulu, and Uhura are delivering a stasis box from the extinct Slaver race on the shuttlecraft Copernicus. When they detect another box and follow its signal, they soon discover that a Kzinti privateer has set a trap. Capturing the Enterprise crew, they discover their box holds a rare find, a shape-shifting Slaver weapon. Now Spock and the others must keep the Kzinti from returning to their government with the weapon.
Beaming down to a planet to search for the crew of the missing ship Ariel, the U.S.S. Enterprise crew is captured by a race of super-intelligent slug creatures and become part of a zoo collection. They find the missing crew also trapped as prisoners in the alien zoo. Now they must somehow establish communications with their evolved slug-like captors who think of them as primitive animals.
The U.S.S. Enterprise hosts Commander Ari bn Bem, an arrogant member of a neutral race from the newly-contacted planet Pandro. However, Bem endangers all of their lives when he conducts a test of suitability upon Kirk and Spock during an exploratory mission. This occurs on a planet of primitive natives under the guardianship of a noncorporeal being.
After avoiding a Romulan ambush by three of their warships, the U.S.S. Enterprise enters a strange energy cloud. The gaseous cloud affects the ship's computer turning it insane. With the crew at the mercy of the Enterprise's computer, it indulges in a series of increasingly aggressive practical jokes.
Backtracking a mysterious alien probe, the U.S.S. Enterprise encounters a ship in the shape of a giant feathered serpent, which turns out to be Kukulkan, a god of ancient Mayan-Aztec legend. Its captain, Kukulkan, is actually a very long-lived benevolent entity who wants the humans to worship him just as the Mayans and Aztecs did. He insists on putting Kirk and others through a test to determine if they have grown sufficiently to receive his wisdom.