On August 12, 2011, large masses thought to be meteors land in the oceans near several major coastal cities. The objects are discovered to be spacecraft containing hostile extraterrestrial life. Marines from Camp Pendleton arrive in Los Angeles, including SSgt. Michael Nantz (Eckhart), an Iraq War veteran. Nantz was to begin retirement, but because of the attack, he is made the acting platoon sergeant for 1st Platoon, Echo Company, of the 2nd Battalion 5th Marines.
Prior to the destruction of Krypton, the criminals General Zod (Terence Stamp), Ursa (Sarah Douglas) and Non (Jack O'Halloran) are sentenced to banishment into the Phantom Zone for insurrection and murder, amongst other crimes.
In 1873, New Mexico Territory, an unnamed loner (Daniel Craig) wakes up in the desert being injured with no memory and with a strange metal object on his wrist. After killing three drifters who think he might be worth bounty money, he takes their clothes, weapons and a horse. He wanders into the small town of Absolution where the local preacher Meacham (Clancy Brown) treats his wound. After the stranger subdues Percy Dolarhyde (Paul Dano), a volatile drunk who has been terrorizing the town, Sheriff Taggart (Keith Carradine) recognizes the stranger as Jake Lonergan, a wanted outlaw, and attempts to arrest him. Jake beats up the posse sent to take him in and nearly escapes, but a mysterious woman named Ella Swenson (Olivia Wilde) knocks him out. Taggart prepares to transport both Jake and Percy to Santa Fe for trial.
In the future, humanity is preparing to launch an attack on the homeworld of an alien race called the Formics who had attacked Earth and killed millions. Over the course of fifty years, gifted children are trained by the International Fleet to become commanders of a new fleet for this counter-attack.
In the 23rd century, Earth has become a space-faring federation. While colonizing new planets, humans have encountered an insectoid species known as Arachnids or "Bugs", with their home being the distant world Klendathu. The bugs appear to be little more than killing machines, though there are suggestions that they were provoked by the intrusion of humans into their habitats.
During the SETI program, Earth's scientists send out transmissions (shown to be the Arecibo message) with information about Earth and its inhabitants, DNA structure, etc., in hopes of finding life beyond Earth. They then receive transmissions from an alien source on how to create endless fuel effortlessly. Therefore, the scientists assume that this is a friendly alien species. From a second alien transmission, the scientists receive information about an alien DNA along with instructions on how to splice it with human DNA. A government team led by Xavier Fitch (Ben Kingsley) goes forward with the genetic experiment attempting to induce a female, because a female would have "more docile and controllable" traits. One of the hundred experimental ova produces a girl named Sil, who looks like a normal human but develops into a 12-year-old in 3 months.
Four waves of increasingly deadly attacks have left most of Earth decimated. Against a backdrop of fear and distrust, Cassie is on the run, desperately trying to save her younger brother. As she prepares for the fifth wave, Cassie teams up with a young man who may become her final hope – if she can only trust him.
In Kentucky, a family watches an enormous horde of cattle running past their home, having caught fire, and a flying saucer leaving Earth. The ship explodes before it returns to Mars, and hundreds of other Martian ships leave Mars and head towards Earth.
Wayne Grey (Seann William Scott), a fireman trainee practicing in a shack in the desert near Glen Canyon, Arizona, sees a meteor strike his car and land in an underground cavern. College professor Ira Kane (David Duchovny) and his colleague, geology professor Harry Block (Orlando Jones), investigate, taking a sample of strange blue liquid that oozes from it. Ira discovers that it harbors extraterrestrial single-celled nitrogen-based organisms multiplying exponentially, condensing millions of years of evolution within a matter of hours. The next day, they take the science class to survey the meteor site and find it already surrounded by evolved oxygen-converting fungi and alien flatworms. Ira and Harry discover that the cells and organisms reproduce rapidly through mitosis after seeing one of the flatworms they collected in a jar split into another.
Jonesy, Beaver, Pete, and Henry are four friends on an annual hunting trip in Maine. As children, they all acquired telepathy which they call "the line". A flashback shows them as they save a mentally handicapped boy named Douglas "Duddits" Cavell from bullies and befriend him.
In the town of Glenview, Ohio, Evan Trautwig (Ben Stiller) is an active participant in the community and senior manager of the local Costco store. His life is disrupted when the store's night security guard, Antonio Guzman (Joseph A. Nunez) is murdered. The local police have no leads, and show no interest in investigating further. Determined to find the killer and bring him to justice, Evan decides to form a neighborhood watch. However, he only manages to recruit Bob (Vince Vaughn), a construction worker and loving father; Franklin (Jonah Hill), a high school dropout who dreams of being a police officer but failed the written, physical, and mental-health tests; and Jamarcus (Richard Ayoade), a recent divorcé.
Jarrod and his girlfriend Elaine have flown to Los Angeles for Jarrod's best friend Terry's birthday party. They celebrate with Terry's wife, Candice, and his assistant, Denise. During the party, one of Terry's employees, Ray, welcomes Jarrod to L.A., thinking he has moved there to join Terry's special effects company. During a private argument about whether or not they should move, Elaine reveals she is pregnant.
Americans Ben and Sean (Max Minghella and Emile Hirsch) travel to Moscow to sell their social networking/party locating software. As they approach the airport the plane short circuits due to an electrical storm but regains power. They find their Swedish business partner, Skyler (Joel Kinnaman), has betrayed them and already made a deal with the Russians, using a knockoff application. They go to a nightclub and meet Natalie (Olivia Thirlby), an American, and her Australian friend Anne (Rachel Taylor). The lights go out in the club and everyone heads outside. There, they witness what appears to be an aurora. Balls of light fall from the sky and then fade away. When a policeman investigates he is disintegrated. The invisible entities begin hunting and disintegrating people, sending them into a panic.
The human race has been taken over by small parasitic aliens called "Souls". The Souls travel to distant planets inserting themselves individually into a host body of that planet's dominant species. They are able to access the host's memories, and occupied hosts are identifiable by silver rings that form in the hosts' eyes.
Chapman University hosts a televised interview with psychologist Dr. Abigail Tyler (Milla Jovovich/Charlotte Milchard). She tells a story of a close encounter incident at Nome, Alaska, in October 2000.