In 2009, American geologist Adrian Helmsley meets his friend, Doctor Satnam Tsurutani in India. Santam has discovered that neutrinos from a massive solar flare are acting as microwaves, 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 instigate a catastrophic chain of natural disasters. At the G8 summit in 2010, other heads of states and heads of government are made aware of the situation. They begin a secret project intended to ensure humanity survives, choosing 400,000 people to board a series of gigantic ships to be constructed in the Himalayas. To help fund the venture, additional individuals are allowed to purchase tickets for one billion euros apiece.

In 2012, Jackson Curtis is a writer in Los Angeles who works part-time as a limousine driver for wealthy Russian business Yuri Karpov. Jackson's ex-wife Kate Curtis and their children Noah and Lily 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 believes a theory that suggests the Mayans predicted the world would come to an end in 2012, and claims he has knowledge of a secret "space ship" project and possesses a map of their location. The family returns home as cracks develop along the San Andreas Fault in California and earthquakes occur in the San Francisco Bay area. 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 collapses into the Pacific Ocean.

As millions die in catastrophic earthquakes worldwide, the group flies to Yellowstone to retrieve Charlie's map. The group narrowly escapes as the Yellowstone Caldera erupts. Charlie, who stayed behind to broadcast the eruption, is killed by the blast. Learning the ships 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 An-225, fleeing Las Vegas as it is destroyed. The group flies to China, passing Hawaii as it is obliterated by volcanic eruptions. Also bound for the ships aboard Air Force One are Anheuser, Adrian, and First Daughter Laura Wilson. President Wilson chooses to remain in Washington D.C. to address the world about the coming disasters. He is soon killed by a giant tsunami that sends the USS John F. Kennedy crashing into the White House. With the Vice President dead and the Speaker of the House missing, Anheuser appoints himself acting president. They also learn that the Italian Prime Minister stayed behind in Italy and is soon killed when The Vatican is destroyed in an earthquake.

Arriving in China in a crash-landing that kills Sasha, the group is spotted by helicopters of the Chinese People's Liberation Army. Yuri and his sons, who have tickets, are taken to the ships to be saved, stranding the Curtis family, Gordon, and Tamara, who do not possess tickets. The group is picked up by Nima, a Buddhist monk on the way to the arks. They sneak into an Ark through its hydraulics chamber with the help of Nima's brother Tenzin, a welder for the project.

Meanwhile, Satnam, in his final moments, calls adrian to inform him that an uncharted tsunami is engulfing India and heading towards the arks before he perishes. Anheuser orders the arks sealed, trapping thousands outside. Adrian convinces the G8 leaders to let the remaining people aboard. As the ark's boarding gate is lowered and then raised, Yuri falls to his death while ensuring his two sons board safely, and Gordon falls between the gears and is crushed. A large drill then falls and becomes lodged between the gears, preventing the gate from closing and rendering the ship unable to start its engines.

The tsunami begins flooding the arks, drowning Tamara and setting the ark adrift. Jackson and Noah free the drill from the closing mechanism. The crew regains control of the ark, preventing a fatal collision with Mount Everest.

When the floodwater from the tsunamis 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 data also reveals that the south pole is now located in Northern Wisconsin, though its orientation (true or magnetic) is unspecified. 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 drastically modified African continent.