In the aftermath of the 1996 War, a span of two decades has seen the establishment of the Earth Space Defense (ESD), a global entity created by the United Nations aimed at utilizing advanced technology derived from the defeated aliens. This initiative stands as humanity's shield against potential extraterrestrial threats, marking a significant return to stability among nations after the struggle for survival. With bases set up at crucial points from Area 51 to the Moon, Mars, and even Rhea, along with orbital defense satellites surrounding Earth, mankind is fortified against any possible future invasions.
The narrative unfolds as Director David Levinson embarks on a mission in the African nation of République Nationale d'Umbutu, where he collaborates with warlord Dikembe Umbutu (Deobia Oparei) and Dr. Catherine Marceaux (Charlotte Gainsbourg). Upon their visit to a crashed alien spacecraft, they uncover alarming revelations: the aliens had been drilling and dispatched a distress signal back to their home world prior to being defeated. This scenario complicates matters further, as characters like former U.S. President Thomas Whitmore (Bill Pullman), Dr. Brackish Okun (Brent Spiner), and Umbutu himself are discovered to share a telepathic link to the aliens' collective consciousness, plagued by visions of an enigmatic spherical object.
As tension escalates, an unidentified spaceship materializes from a wormhole near the Moon. In defiance of Levinson's attempts to prevent it, the United Nations Security Council decides to destroy the vessel. American pilots Jake Morrison (Liam Hemsworth) and Charlie Miller (Travis Tope) take decisive action against the orders, collecting Levinson, Marceaux, Umbutu, and federal controller Floyd Rosenberg (Nicolas Wright) aboard a space tug to explore the remnants in the Van de Graaff crater. During their mission, they retrieve a substantial container that holds a sphere. To their shock, an alien mothership—vastly larger than anything previously encountered—descends, obliterating Earth’s defensive systems and drilling towards the core for fuel, thereby presenting a catastrophic threat to the planet.
After barely escaping annihilation, the space tug makes it back to Area 51. Here, Levinson, Whitmore, and General Joshua Adams (William Fichtner) conduct interrogations with an alien captive from the earlier war, unveiling that these extraterrestrials operate under a hivemind, led by a colossal Queen who directs the invasion. This prompts Levinson to propose a bold strategy: eliminating the ruling Queen could immobilize her armies. The ESD, led by Captain Dylan Hiller (Jessie T. Usher), initiates a counteroffensive, only to find themselves caught in a devastating ambush within the mothership, with only a handful of fighters, including Dylan, Jake, and Rain Lao (AngelaBaby), managing to survive.
Back at Area 51, a dramatic moment arises when Okun unveils the sphere they uncovered, which reveals its purpose: to aid survivors in evacuating to a safe haven while uniting them for an offensive against the aliens, referred to ominously as "Harvesters." Meanwhile, chaos ensues in the mothership; the surviving ESD pilots commandeer enemy crafts, with Dylan, Jake, Charlie, and Rain pursuing the Queen’s ship intent on reaching Area 51 to extract the potential knowledge of the safe haven.
Aware that the Queen has discovered the sphere's whereabouts, the ESD devises a strategic plan to hide the sphere in isolation and use a decoy aboard Jake's shuttle to ensnare the Queen's ship. Whitmore takes a significant risk, volunteering to pilot the decoy on a mission that could end in catastrophe, leading the Queen's ship into a deadly trap, which he detonates, sacrificing himself in a bid to destroy the enemy craft. However, the Queen survives the initial explosion, leading to a fierce confrontation culminating in her ultimate elimination. As a result, the remaining alien units are rendered inactive, and the mothership retracts, ceasing its drilling operations and departing Earth’s atmosphere.
In the wake of these harrowing events, it is discovered that the sphere has significant plans for humanity: it seeks to enlist Earth's forces in a resistance against the Harvesters, preparing for an impending war that could shape the fate of the cosmos.