Three years into their five-year mission to explore uncharted space, the crew of the USS Enterprise arrives at Starbase Yorktown, a massive space station, for resupply and shore leave. Captain James T. Kirk, feeling disconnected from his late father’s legacy, considers a promotion to Vice Admiral and a life grounded in the station. Meanwhile, Spock, facing a personal crossroads, contemplates leaving Starfleet to help rebuild New Vulcan. However, their reflections on the future are interrupted when the Enterprise is dispatched on a rescue mission after receiving an escape pod carrying an alien, Kalara, who claims her ship is stranded on Altamid, a planet in a nearby uncharted nebula.

Arriving at Altamid, the Enterprise is viciously attacked by a swarm of alien ships led by Krall, a ruthless enemy with a vendetta against the Federation. The swarm cuts through the Enterprise's defenses, leading to the ship's catastrophic failure and forced evacuation. With the Enterprise crew scattered across the planet and the ship destroyed, they must survive a hostile environment and regroup. They encounter Jaylah, a resourceful alien inhabitant who agrees to help them. While the crew throws together makeshift defenses and attempts to understand Krall’s motivations, Kirk must find a way to stop Krall from launching a bio-weapon attack that could lead to millions of deaths and the destruction of the Federation.