Jack Hall (Dennis Quaid) is a paleoclimatologist who is on an expedition in Antarctica with two colleagues, Frank (Jay O. Sanders) and Jason (Dash Mihok), drilling for ice core samples on the Larsen Ice Shelf for the NOAA. The ice shelf suddenly breaks off from the rest of the continent, and Jack almost falls to his death. Jack presents his findings on global warming at a United Nations conference in New Delhi. Jack found that 10,000 years ago, a global warming changed the earth's climate into the Ice Age. Jack says that it could happen again in maybe 100 to 1,000 years from now if humans don't stop polluting the atmosphere. Most of the diplomats, including the Vice President of the United States (Kenneth Welsh), are unconvinced by Jack's theory. At the conference, Jack meets Professor Terry Rapson (Ian Holm) of the Hedland Climate Research Centre in Scotland, who is keeping track of the world's ocean currents. Terry tells Jack that the melting of the polar ice caps has poured fresh water into the oceans and diluted the salt level balance, which has caused the temperature of the ocean currents to drop 13 degrees.
Two buoys in the North Atlantic simultaneously show a massive drop in the ocean temperature, and Rapson concludes that melting of the polar ice has begun disrupting the North Atlantic current. He calls Jack, whose paleoclimatological weather model holds reconstructional data of the climate change that caused the first Ice Age, to predict what will happen. Jack believed that the events would not happen for a hundred or a thousand years, but he, Frank, Jason, and NASA's meteorologist Janet Tokada (Tamlyn Tomita) build a forecast model with his, Rapson's, and Tokada's data.
All over Earth, the climate system changes for the worst. Tokyo is hit by softball size hail; it begins to snow in New Delhi; and Los Angeles is destroyed by a group of huge F5 tornadoes that hit all at the same time. The U.S. President (Perry King), authorizes the FAA to suspend air traffic over the United States due to severe turbulence. As three RAF helicopters fly to evacuate the British Royal Family from Balmoral Castle in Scotland, they enter the eye of a very massive hurricane-like superstorm, that causes a temperature drop of -150 °F that freezes their fuel lines and rotors, causing them to crash and quickly freeze to death.
Meanwhile, Jack's son, Sam, (Jake Gyllenhaal) is in New York City for an academic competition with his friends Brian and Laura (Arjay Smith and Emmy Rossum), where they also befriend a student named J.D. During the competition, the weather becomes massively violent with intense winds and flooding rains. Sam calls his father, making a promise to be on the next train home. Unfortunately, the storm worsens, forcing subways and Grand Central Station to close when they flood.
Jack sees the President and gives him the bad news that his estimate of years is now down to days before the planet enters a new Ice Age. Jack advises the President to evacuate everybody in the southern states to Mexico, because it is too late to evacuate the people in the northern states. The Vice President says he's not amused by Jack's supposed sarcasm and Jack leaves for New York to find his son.
As the storm worsens in Manhattan, a storm surge almost 40 feet (about half the height of the Statue of Liberty) impacts the island, causing major flooding. Sam and his friends are able to seek refuge in the New York Public Library. As they make their way to the front doors, Laura cuts her leg on a piece of jagged metal attached to a cab. She ignores the injury and helps a woman and her children get out of a flooding taxi.
Survivors in the Northern United States are forced to flee south, with some Americans illegally crossing the border into Mexico. Jack sets off for Manhattan to find his son, accompanied by Frank and Jason. Their truck crashes into a snow-covered tractor-trailer just past Philadelphia, so the group continues on snowshoes. During the journey, Frank falls through the glass roof of a snowbound shopping mall. As Jason and Jack try to pull Frank up, the glass under them continues to crack; Frank sacrifices himself by cutting the rope and he falls to his death.
The U.S. President's helicopter is caught in the superstorm, killing everyone on board, leaving the U.S. Vice President in charge. With much of the population of the southern half of the United States at the border with Mexico, the VP agrees to forgive a large amount of debt owed by the Mexican government to allow people to cross the border to safety.
Inside the library, Sam advises everyone of his father's instruction to stay indoors. Few listen, and the small group that remains burns books to keep warm and breaks into the library's vending machine for food. Laura is afflicted with blood poisoning when the cut she received turns septic, so Sam, Brian, and J.D. must search for penicillin in a Russian cargo ship that drifted inland, and are attacked by escaped wolves from the New York Zoo. Just then, the eye of the North American superstorm begins to pass over the city with its -150 °F instant freeze temperatures, and the entire New York City skyline begins to freeze solid, buildings and air alike. The three return to the library with medicine, food, and supplies, making it to safety.
During the deep freeze, Jack and Jason take shelter in an abandoned Wendy's restaurant. Jason had succumbed to the extreme cold and wind and collapsed. In desperation, Jack dropped him into the restaurant's kitchen through a vent and holed up until the storm's eyed passed. They resume their journey, finally arriving in New York City. They find the library buried in snow, but find Sam's group alive and are rescued by U.S. Army soldiers flying UH-60 Blackhawk helicopters.
In Mexico, the new President orders search and rescue teams to look for other survivors, having been given hope by the survival of Sam's group. Several more groups are found on top of Manhattan skyscrapers and are also rescued. The movie concludes with two astronauts looking down at Earth from the International Space Station, showing most of the northern hemisphere covered in ice, including all of the United States north of the southern states, and a major reduction in pollution.