Caltech seismologist Dr. Lawrence Hayes and his colleague Dr. Kim Park are at Hoover Dam testing a new earthquake predicting model when a nearby and previously unknown fault ruptures, triggering a 7.1 magnitude earthquake that collapses the dam; Park is killed shortly after rescuing a child. Hayes discovers that the entire San Andreas Fault is shifting and will soon cause a series of major earthquakes, potentially destroying cities along the fault line. He begins racing to warn the population of California along with his students Alexi and Phoebe and reporter Serena Johnson.
When a 9.1 magnitude earthquake devastates Los Angeles and San Francisco, Ray Gaines, a Los Angeles Fire Department helicopter-rescue pilot going through a divorce from his wife Emma, finds himself rescuing her from a skyscraper in Los Angeles, and their daughter Blake becomes trapped in San Francisco in the office of Emma's boyfriend, Daniel Riddick, who then abandons her. Ben Taylor, a British engineer seeking employment, and his younger brother Ollie rescue Blake and they reach Chinatown, successfully calling her parents for help.
Ray and Emma attempt to reach San Francisco in Ray's helicopter until it suffers a gearbox failure, forcing them to make an emergency landing at a shopping mall in Bakersfield. Amid the chaos of looting, Ray steals a Ford F-150 to continue the journey. The pair encounter a couple broken down on the side of the road, shortly before the San Andreas Fault, which has reopened and blocked the road. Ray and Emma exchange the truck for an airplane the couple owns. As Blake, Ben, and Ollie attempt to reach Nob Hill to signal the pair after finding their previous meeting point at Coit Tower engulfed in flames, Ray and Emma are forced to parachute into AT&T Park just before a 9.6 magnitude quake hits, becoming the largest recorded earthquake in history.
As the quake subsides, having destroyed much of the city, Ray and Emma commandeer a boat to reach the group, only to realize a tsunami is approaching San Francisco Bay. They manage to cross the wave before it crests, barely avoiding a huge cargo ship caught up in the wave. The ship snaps the Golden Gate Bridge's center span in half, killing everyone on the bridge, including Daniel, and the wave swamps the ruined city, killing thousands more. Blake, Ben, and Ollie enter the Gate, a building whose construction Daniel had been overseeing, but are still caught by the wave. As the building begins to collapse, trapping Blake underwater, Ray dives in, rescues her, and begins performing CPR. Emma crashes the boat through a window and drives the four of them out of the collapsing building as Ray resuscitates Blake.
The survivors regroup at a relief camp, where the reconciled Ray and Emma talk about their future. On the remains of the Golden Gate Bridge an American flag unfolds, giving hope that the city will recover and rebuild, as rescue vehicles descend on the radically altered landscape of the San Francisco Bay Area, which has now extended from San Jose to Santa Cruz, turning the San Francisco Peninsula into an island.
Dwayne Johnson as Raymond "Ray" Gaines, a Los Angeles Fire Department helicopter-rescue pilot
Carla Gugino as Emma Gaines, Ray's estranged wife
Alexandra Daddario as Blake Gaines, Ray and Emma's daughter
Hugo Johnstone-Burt as Ben Taylor, an English engineer and Blake's love interest
Art Parkinson as Ollie Taylor, Ben's younger brother
Ioan Gruffudd as Daniel Riddick, Emma's boyfriend and owner of a civil engineering firm
Archie Panjabi as Serena Johnson, a news reporter
Paul Giamatti as Dr. Lawrence Hayes, a Caltech seismologist
Will Yun Lee as Dr. Kim Park, a Caltech seismologist, and Lawrence's research partner and closest friend
Kylie Minogue as Susan Riddick, Daniel's sister
Alec Utgoff as Alexi, Lawrence's student
Todd Williams as Marcus Crowlings, a fellow Los Angeles Fire Department member
Marissa Neitling as Phoebe, Lawrence's student
Matt Gerald as Harrison Rhodes, a fellow Los Angeles Fire Department helicopter-rescue pilot
Colton Haynes as Joby O'Leary, a fellow Los Angeles Fire Department helicopter-rescue pilot
Arabella Morton as Mallory Gaines, Ray and Emma's other daughter and Blake's sister, who drowned in a rafting accident. This is shown in a flashback.
Morgan Griffin as Natalie
Julian Shaw as Stoner
Joey Vieira as Man in parking garage