Twenty years following a catastrophic alien invasion, the United Nations has established the Earth Space Defense (ESD), a comprehensive global initiative aimed at reverse-engineering alien technology and functioning as Earth’s first line of defense against future extraterrestrial threats. The primary military force operates out of military bases situated on the Moon, Mars, and Rhea, utilizing salvaged equipment from prior alien forces. The ESD Headquarters now resides at the infamous Area 51 in Nevada.
As the world prepares to commemorate the 20th anniversary of their survival on July 2, 2016, ESD Director [David Levinson](jeff-goldblum) finds himself in the provincial African nation of Republique Nationale D'Umbutu. He is in discussions with Dr. Catherine Marceaux (Charlotte Gainsbourg), who works at Area 51 specializing in telepathy, and the local warlord, Dikembe Umbutu (Deobia Oparei). They uncover an undamaged alien destroyer, initially stopped in its tracks when the mother ship was obliterated during the first conflict. Recently, the lights on the destroyer have activated, signaling a possible threat. Upon investigation, they discover that the alien crew sent a distress signal to their home world before their defeat. Meanwhile, former U.S. President [Thomas Whitmore](bill-pullman), who once led the nation through the first invasion, shares a telepathic connection with the aliens due to his past encounters with them.
At Area 51, Dr. Brakish Okun (Brent Spiner) awakens after two decades of being in a coma, his mind still recovering from a Harvester's psychic assault. In another part of the moon base, Jake Morrisson ([Liam Hemsworth](liam-hemsworth)) works as a space tug operator. He is engaged to [Patricia Whitmore](maika-monroe), the former First Daughter and now a speechwriter at the White House. Jake's history with Captain Dylan Dubrow-Hiller (Jessie T. Usher)—the son of the deceased hero Steven Hiller—has become strained after a previous incident while they were both test pilots for Earth's defense initiatives.
On July 3, an unfamiliar spherical ship appears from a wormhole near the ESD’s Moon base. Levinson believes the vessel belongs to another alien race possibly seeking peaceful contact. However, the world’s Security Council, driven by fear, decides to destroy it. Back on Earth, Patricia learns that the ESD has shot down what they assumed to be the enemy vessel.
Dr. Okun, now back in action, aligns with the ESD just as pilots Jake and his best friend, Charlie Miller (Travis Tope), go against orders to collect Levinson and his team, including Umbutu and accountant Floyd Rosenberg (Nicolas Wright), in a space tug. Together, they venture to the wreckage of the alien craft, uncovering a spherical container which Levinson decides to bring back for further research.
On July 4, a massive alien mothership, measuring over 3,000 miles in diameter, materializes and obliterates Earth's defenses, including the Moon base, prompting Dylan and the pilots to retreat. The tug piloted by Jake narrowly escapes the chaos, but debris from the mothership wreaks havoc across Europe as it descends toward the Atlantic Ocean to extract the planet’s core energy, a process that threatens to collapse Earth's magnetic field.
Meanwhile, Whitmore interrogates an alien captive, uncovering that the invaders operate with Eusociality, answering to a colossal Queen aboard the mothership. Levinson posits that destroying the Queen would halt the invasion and the ESD, led by Captain Dylan, embarks on a counteroffensive. Unfortunately, they fall into a trap and sustain heavy losses.
Back at Area 51, Okun activates the container, revealing a benevolent AI sphere designed to rescue survivors from worlds targeted by the aliens. The moment the sphere activates, the mothership’s Queen is notified, leading her to prepare for an assault. As the threat escalates, Jake, Dylan, and other survivors hijack enemy ships to pursue the Queen, who is en route to reclaim the sphere.
Aware of the Queen's looming threat, the forces at ESD implement a strategic plan to hide the sphere while using a decoy to draw the Queen into a trap filled with fusion explosives. Against his daughter's wishes, Whitmore sacrifices himself in a daring mission to detonate the explosives, maiming the Queen, yet she manages to survive thanks to her energy shield. In a climactic fight, Patricia pilots a fighter jet to disable the shield, allowing Dylan and his team to conclude the battle by taking down the Queen. With her demise, the mothership retreats, and Okun reveals the sphere has offered humanity advanced technology to prepare them for a counterstrike against the alien Harvesters.
