Although Captain James T. Kirk was understandably traumatized by his fateful reunion on Camus II with his old flame Dr. Janice Lester on stardate 5298.5 (2269) — Lester nearly succeeded in permanently stealing Kirk's identity by means of an ancient mind-transference device — he immediately returned to the bridge of the U.S.S. Enterprise to embark on the final months of his historic five-year mission of exploration. On stardate 5221.3 (2269), Kirk presided over the discovery of a 300-million-year-old alien starship, and encountered the hostile, noncorporeal entity responsible for that vessel's destruction. On stardate 5554.4, on the newly discovered world of Phylos, Kirk had a second encounter with a relic from the era of Earth's Eugenics Wars in the person of Dr. Stavos Keniclius 5, the clone of the original Dr. Stavos Keniclius. Keniclius 5 abducted — and nearly murdered — Spock as part of his plan to raise a cloned army intended to force "peace? upon the galaxy. Fortunately, Kirk succeeded in rescuing Spock after persuading Keniclius 5 that the existence of the United Federation of Planets, which did not exist during the twenty-first century, when the original Keniclius lived, made such draconian measures unnecessary.

Shortly thereafter, Kirk and his crew were placed on trial for the crimes of all mankind on stardate 1254.4 (2269), and ultimately prevailed. Stardate 5267.6 found Kirk and his crew stranded in a pocket universe known as Elysia, along with the Klingon Captain Kor and the crew of his battle cruiser, the I.K.S. Klothos; if not for Kirk's considerable powers of persuasion, Kor and his people would have been placed in hibernation for a century by the violence-averse Elysians. On stardate 5577.7, Kirk made first contact with the Terratins, the descendants of the lost human colony of Terra Ten ("Terratin?), all of whom had been shrunk to tiny size by the spiroid epsilon waves prevalent on the surface of their adopted planet, the only world orbiting the distant star Cepheus; after recovering from being briefly shrunk to the Terratins' tiny size, Kirk and his crew relocated the Terratins to the far safer planet Verdanis. Along with Spock, Kirk briefly became a water-breather on the pelagic planet Argo on stardate 5499.9.

On stardate 3183.3, Kirk encountered another energy-based intelligence, which commandeered the Enterprise's computer systems and began playing a relentless series of practical jokes on the ship's captain and crew; by pretending to be deathly afraid of the energy field from which the entity had come, Kirk fooled the creature into taking the Enterprise inside the field, which swiftly reabsorbed the entity. When an outbreak of so-called "auroral plague? swept through the Enterprise on stardate 5275.6, Kirk was among those rendered comatose by the disease, which was reversed in the nick of time by Dr. McCoy. As he came out of his disease delirium, Kirk helped Spock and McCoy clear McCoy's name by proving to the angry authorities of the planet Dramia II that an outbreak of the same disease 19 years earlier had actually been caused by a planetary aurora, and then spread by a Dramian named Demos, rather than by McCoy. Stardate 6063.4 not only saw Kirk wrestling a lethal, electricity-spewing power-cat from Capella IV, it also once again brought the captain into contact with a genuine, bona fide god — in the person of the Mayan feathered serpent deity Kukulkan, an ancient starfaring being responsible for the dragon myths in many Earth cultures. Fortunately Kirk succeeded in persuading Kukulkan that humans no longer had need of gods, and wasn't forced to cripple him as had been the case with the Greek god Apollo during a similar encounter on Pollux IV two years earlier.

On stardate 6770.3 (2269), the Enterprise's accidental passage through the Beta Niobe nova remnant into an adjacent antimatter universe in which time flowed backward caused Kirk and his entire crew to regress to childhood, forcing the visiting Commodore Robert April to take command temporarily during the starship's perilous return home. With the help of the pattern traces stored in the Enterprise's transporter, Kirk and the rest of his crew were subsequently returned to their normal ages, ready to resume their mission of galactic exploration as an eventful 2269 drew to a close.

After the conclusion of the Enterprise's historic five-year mission, Kirk returned to Earth and accepted a promotion to the rank of admiral. He remained in an unsatisfying desk job, with no ship of his own to command, until stardate 7410.2 (2271), when he convinced his Starfleet Command — in the person of a difficult-to-persuade senior admiral named Heihachiro Nogura —to give him command of the newly refitted Enterprise in order to face the approaching danger of the destructive cosmic entity known as V'Ger.