In 2009, American geologist Adrian Helmsley learns from a colleague, Dr. Satnam Tsurtuani, at an underground copper mine in India that neutrinos from a massive solar flare are acting as microwave radiation, causing the temperature of the Earth's core to increase rapidly. Adrian informs White House Chief of Staff Carl Anheuser and US President Thomas Wilson that this will trigger a catastrophic chain of natural disasters. At the G8 summit in 2010, other heads of state and heads of government are made aware of the situation. They begin a massive, secret project intended to ensure the survival of humanity. Approximately 400,000 people are chosen to board a series of ships (called arks) to be constructed in the Himalayas. The majority of tickets aboard the ships are reserved for heads of state, government officials and selected individuals chosen for their skills, while additional funding for the project is raised by selling tickets to the private sector at the price of 1 billion euros per person.

In 2012, Jackson Curtis is a writer in Los Angeles who works part-time as a limousine driver for Russian billionaire Yuri Karpov. Jackson's ex-wife Kate and their children Noah and Lilly live with her boyfriend, plastic surgeon and amateur pilot Gordon Silberman. Jackson takes Noah and Lily on a camping trip to Yellowstone National Park, where they meet Charlie Frost, a conspiracy theorist living as a hermit and hosting a radio show from the park. Charlie references a theory that suggests the Mayans predicted the world would come to an end in 2012, and claims he has knowledge and a map of the secret ark project. The family returns home as cracks develop along the San Andreas Fault in California and large earthquakes occur in many places along the West Coast. Jackson grows suspicious and rents a plane to rescue his family. He collects his family and Gordon when the Earth's crust displacement begins and they narrowly escape Los Angeles as it crumbles into the Pacific Ocean.

As millions die in cataclysmic earthquakes worldwide, the group flies to Yellowstone to retrieve Charlie's map. After retrieving the map, the group narrowly escapes as the Yellowstone Caldera erupts. Charlie, who stayed behind to broadcast the eruption, is killed in the blast. Learning that the arks are in China, the group lands in Las Vegas, where they meet Yuri, his sons, girlfriend Tamara, and pilot Sasha. They join the group and secure an Antonov 225 aircraft, fleeing just as Las Vegas is destroyed. They now head to China, also bound for the arks aboard Air Force One are Anheuser, Adrian, and First Daughter Laura Wilson. President Wilson chooses to remain in Washington D.C., and is soon killed by a mega tsunami that sends the USS John F. Kennedy crashing into the White House. With the Vice President also dead and the Speaker of the House missing, Anheuser takes over as acting president.

Arriving in China in a crash-landing that kills Sasha, the group is spotted by the Chinese People's Liberation Army. Yuri and his sons, possessing tickets, are taken to the ships. The Curtis family, Gordon, and Tamara, who do not have tickets, are picked up by Nima, a Buddhist monk on his way to the arks. They stowaway aboard an ark with the help of Nima's brother Tenzin, who has been working on the ark project. A mega tsunami approaches the site as tens of thousands are still attempting to board the final ark, and a large impact driver becomes lodged between the gears of the ark's hydraulics chamber, preventing a boarding gate from closing and rendering the ship unable to start its engines. In the ensuing chaos, Yuri, Gordon, and Tamara are killed, and the flooded ark is set adrift. Jackson and Noah free the impact driver from the closing mechanism, and the crew regains control of the ark, preventing a fatal collision with Mount Everest.

When the global floodwater from the tsunamis eventually recedes, satellite data shows that Africa's elevation rose in relation to sea level, and the Drakensberg mountains in KwaZulu Natal are now the highest on the planet. The scientists are sure that the rest of the land on earth will soon rise above sea level, too. As three arks set sail for the Cape of Good Hope, Jackson reconciles with his family and Adrian starts a relationship with Laura. The movie ends with a view of the Earth from space, showing a vastly different continental landscape.