In 1996, treasure hunter Brock Lovett and his team aboard the research vessel Akademik Mstislav Keldysh search the wreck of RMS Titanic for a necklace with a rare diamond, the Heart of the Ocean. They recover a safe containing a drawing of a young woman wearing only the necklace dated April 14, 1912, the day the ship struck the iceberg. Rose Dawson Calvert, the woman in the drawing, is brought aboard Keldysh and tells Lovett of her experiences aboard Titanic.
On July 2, a 500 km wide alien mothership enters Earth's orbit and deploys several dozen saucer-shaped "destroyer" spacecraft, each 15 miles (24 km) wide. As they take position over some of Earth's major cities, David Levinson (Jeff Goldblum), an MIT graduate working for a cable company in New York City, discovers hidden transmissions in Earth's satellites which he realizes is a timer counting down to a coordinated attack by the aliens. With the support of his estranged wife Constance Spano (Margaret Colin), the White House Communications Director, he and his father Julius (Judd Hirsch) gain entrance into the Oval Office to notify President Thomas J. Whitmore (Bill Pullman) about the attack. Whitmore orders large-scale evacuations of the targeted cities, but the aliens attack with advanced directed-energy weapons before these can be carried out. Whitmore, portions of his staff, and the Levinsons narrowly escape aboard Air Force One as Washington, D.C. is destroyed.
In 2009, American geologist Adrian Helmsley visits astrophysicist Satnam Tsurutani in India and learns that neutrinos from a massive solar flare are causing the temperature of the Earth's core to rapidly increase. Arriving at a party in Washington, D.C, Helmsley presents his information to White House Chief of Staff Carl Anheuser, who takes him to meet the President.
Dr. Ryan Stone (Sandra Bullock) is a biomedical engineer aboard the NASA space shuttle Explorer for her first space mission, STS-157. Veteran astronaut Matt Kowalski (George Clooney) is commanding his final mission. During a spacewalk to service the Hubble Space Telescope and Stone's upgrades to the Telescope, Mission Control in Houston warns the team about a Russian missile strike on a defunct satellite, which has inadvertently caused a chain reaction forming a cloud of debris in space. Mission Control orders that the mission be aborted and the crew begin re-entry immediately because the debris is speeding towards the shuttle. Communication with Mission Control is lost shortly thereafter.
The narrator (Morgan Freeman) explains how humans were unaware that intelligent extraterrestrials were making plans to occupy Earth. Ray Ferrier (Tom Cruise) is a divorced crane operator longshoreman who works at a dock in Bayonne, NJ. Ray is estranged from his children. His former wife, Mary Ann (Miranda Otto), later drops off the children, 10-year-old daughter Rachel (Dakota Fanning) and teenage son Robbie (Justin Chatwin), at Ray's house in Bayonne on her way to visit her parents in Boston. Unexplained changes in the weather occur, emitting lightning that strikes multiple times in the middle of an intersection and disrupting all electrical technology in the area.
In 2009, a genetically re-engineered measles virus, originally created as a cure for cancer, turns into a lethal strain which kills 90% of those it infects, and mutates the remaining 10% into predatory, nocturnal mutants called "Darkseekers" who are extremely vulnerable to sunlight and other sources of UV. Three years after the outbreak, US Army virologist Lieutenant Colonel Robert Neville (Will Smith) lives an isolated life in the ruins of New York City, which is now deserted, unsure if any other uninfected humans are left in the world.
A massive meteor shower destroys the orbiting Space Shuttle Atlantis and bombards a swath of land from America's East Coast from South Carolina through Finland. NASA discovers that a rogue asteroid the size of Texas passed through the asteroid belt and pushed forward a large amount of space debris. The asteroid will collide with Earth in 18 days, causing an extinction event that will even wipe out bacteria. NASA scientists, led by Dan Truman, plan to trigger a nuclear detonation 800 feet (240 m) inside the asteroid to split it in two, driving the pieces apart so both will fly past the Earth. NASA contacts Harry Stamper, considered the best deep-sea oil driller in the world, for assistance. Harry travels to NASA with his daughter Grace, to keep her away from her new boyfriend and one of Harry's drillers, A. J. Frost. Harry explains he will need his team, including A. J., to carry out the mission. They agree to help, but only after their list of unusual rewards and demands are met.
A zombie outbreak erupts in metropolitan areas around the world; those bitten by the creatures become zombies themselves within twelve seconds. Retired UN investigator Gerry Lane, his wife Karen, and their two daughters manage to escape the outbreak in Philadelphia and take shelter with a family in Newark while waiting for special evacuation the next day, thanks to Gerry's friend UN Deputy Secretary-General Thierry Umuntoni. They find a shelter for the night while waiting for a rescue helicopter. Their hosts choose not to accompany them when they flee the next day, and are subsequently bitten and changed by zombies. Their son, Tommy, manages to escape, and Gerry's family takes him in. They are flown to an offshore U.S. Navy carrier group near New York where Umuntoni is overseeing the remaining worldwide governments' reactions.
In 1954, a nuclear bomb is detonated at the moment a giant creature emerges from the ocean. In 1999, Project Monarch scientists Ishiro Serizawa and Vivienne Graham investigate a colossal skeleton unearthed in a collapsed mine in the Philippines. They find two spores; one dormant and one hatched that made a trail into the sea. In Japan, the Janjira Nuclear Power Plant experiences unusual seismic activity and Supervisor Joe Brody sends his wife Sandra and a team of technicians into the reactor. A tremor breaches the reactor, leaving Sandra and her team unable to escape while the plant collapses.
In June 1969, 5-year-old Jo Thornton (Alexa Vega), her parents, and the family dog Toby seek shelter in a storm cellar as a powerful F5 tornado. This tornado is so strong that the storm cellar door is ripped off, and Jo's father (Richard Lineback) is pulled into the storm to his death. Jo, her mother (Rusty Schwimmer), and Toby survive.
Raymond "Ray" Gaines (Dwayne Johnson) is a Los Angeles Fire Department Air Rescue pilot in the midst of a divorce from Emma (Carla Gugino) and planning a trip to San Francisco with his daughter Blake (Alexandra Daddario).
In 2013, Earth's coastal cities come under attack from Kaijus, colossal beasts that periodically emerge from a dimensional portal on the Pacific Ocean floor called "The Breach." To fight them, the Pacific Rim nations build the Jaegers, equally colossal humanoid war machines. Each Jaeger is controlled by two or more pilots whose brains are linked, called "drifting" to share the heavy mental load of operating the machine. The Jaegers are initially effective, but many are destroyed as the Kaijus grow more powerful and their attacks become more frequent. In 2025, the participating governments deem the Jaeger program unsustainable and discontinue it in favor of building defensive coastal walls. The four remaining Jaegers are redeployed to Hong Kong to protect the coast until the walls are completed. Jaeger commander Stacker Pentecost resolves to make a last-ditch attempt to end the Kaiju threat by destroying The Breach with a nuclear weapon, even though past nuclear strikes on the portal have been unsuccessful.