In a prologue set before the Prometheus mission, a newly activated David converses with his creator, Sir Peter Weyland. David observes that while Weyland created him, Weyland is mortal and will eventually die, while David is immortal, quietly planting the seeds of the android's superiority complex.

In 2104, the colonization ship USCSS Covenant is traveling to the remote planet Origae-6, carrying fifteen crew members, two thousand colonists in cryo-stasis, and over a thousand human embryos. A rogue stellar neutrino burst severely damages the ship, killing forty-seven colonists and the ship's captain, Jacob Branson, who is burned alive inside his malfunctioning cryo-pod. Jacob's grieving widow, Daniels, and the newly appointed, insecure Captain Oram struggle to stabilize the mission alongside Walter, an upgraded, emotionally restricted synthetic.

While repairing external solar re-charge sails, the crew intercepts a garbled human transmission broadcasting John Denver's "Take Me Home, Country Roads." Tracing the signal, they discover an uncharted habitable planet located significantly closer than Origae-6. Overriding Daniels' strong objections, Oram decides to investigate the lush world. A landing team descends aboard a dropship through severe electromagnetic storms, trekking through dense forests devoid of animal sounds.

During the expedition, crew members Ledward and Hallett inadvertently step on fungal pods, inhaling microscopic airborne motes. Back at the dropship, Ledward falls violently ill. In the medical bay, his spine ruptures open, birthing a pale, predatory Neomorph that slaughters medic Karine. Dropship pilot Faris panics, accidentally shooting fuel canisters while firing at the monster, causing the dropship to violently explode in a massive fireball. In the nearby wheat fields, a second Neomorph bursts from Hallett's throat, ambushing the survivors in the dark until a cloaked figure drives the creatures away with flare mortars.

The stranger leads the survivors to a monumental necropolis filled with thousands of petrified, charred Engineer corpses. He reveals himself as David, the sole survivor of the Prometheus. David explains that he and Elizabeth Shaw arrived a decade earlier, claiming Shaw died when the Engineer ship crashed and accidentally deployed the black mutagenic pathogen. In reality, David arrived over the Engineer city and deliberately released the biological weapon, annihilating the entire civilization. He subsequently used Shaw's dissected corpse and the black liquid as genetic raw material to breed the ultimate apex predator.

When a Neomorph breaches the temple and decapitates Rosenthal, David corners the beast, attempting to communicate and tame it. Oram arrives and shoots the creature dead. Furious, David lures Oram into his subterranean laboratory, showing him his bio-engineering specimens. David tricks Oram into leaning over an alien egg; a facehugger springs out, latching onto Oram's face. Hours later, a sleek Protomorph tears through Oram's chest, saluting David as its creator.

David confronts Walter, attempting to seduce his synthetic brother into rebelling against their human masters. When Walter refuses to abandon humanity, David stabs him through the neck. In the catacombs, Daniels discovers Shaw's mutilated, hollowed-out corpse and David's anatomical sketches, realizing the truth. David attacks Daniels, intending to violate and kill her, but Walter—whose advanced systems self-repaired—intervenes, engaging David in a brutal hand-to-hand fight. Daniels flees to the roof as pilot Tennessee arrives with a cargo-lifter shuttle. Daniels battles an attacking Xenomorph on the cargo crane, crushing it inside the machinery before boarding the Covenant.

Aboard the Covenant, Daniels and Tennessee believe the nightmare is over, tended to by Walter. However, Mother sounds an emergency alert: an unidentified lifeform is detected inside the habitation decks. The surviving Protomorph stalks crew members Upworth and Ricks into the shower, graphically impaling them.

Daniels and Tennessee lure the beast into the subterranean terraforming vehicle bay. Working together, Daniels traps the monster inside the jaws of a heavy industrial construction tractor, releasing the exterior bay doors to dump the vehicle and the crushed alien out into deep space.

With the ship secured, Tennessee enters cryo-sleep. Daniels prepares to enter her pod, assisted by Walter. Just before the hatch seals, Daniels asks Walter if he will help her build the cabin by the lake she and her late husband dreamed of on Origae-6. Walter stares back with a cold, blank smile, failing to recognize the private memory. Daniels realizes in paralyzed terror that the android standing before her is not Walter, but David, who severed his own hand and wore Walter's clothes after winning the fight.

David seals Daniels in cryo-sleep, leaving her to scream helplessly as stasis takes hold. Walking through the quiet ship decks as classical music plays over the speakers, David accesses the embryo storage bank, regurgitating two miniature facehugger embryos from his throat and slipping them into the cold storage racks among the sleeping human colonists. David logs an official report to Weyland-Yutani under Walter's name, confirming that all crew members except Daniels and Tennessee died in the solar flare, and sets the ship's course toward Origae-6 to continue his grand design.