At a star party on May 10, 1998, amateur astronomer Leo Biederman (Wood) discovers an unusual object near the stars Mizar and Alcor, and alerts professional astronomer Marcus Wolf (Charles Martin Smith) at a local observatory. After learning that the object is a comet and working out its orbit Wolf realizes that the comet will impact with Earth but dies in a car accident before he can alert the world.

A year later, MSNBC reporter Jenny Lerner (Leoni) investigates the resignation of the United States Secretary of the Treasury and his connection to an "Ellie". She discovers that Ellie is not a mistress but "E.L.E.", an acronym for "extinction-level event". Because of Lerner's investigation, President of the United States Tom Beck (Freeman) announces the grim facts: The comet—named Wolf-Biederman—is 7 miles (11 km) wide, large enough to destroy civilization when it strikes Earth on August 16, 2000. Eight months ago the United States and Russia began secretly constructing in orbit Messiah, the largest spacecraft ever built. They plan to send Messiah to destroy the comet with nuclear weapons. Life changes drastically worldwide, and Leo and Lerner both become celebrities.

After landing on the comet Messiah's crew plants the bombs into its surface, but one crew member dies and another is seriously injured. When the bombs are detonated, Messiah is damaged and contact with Earth is lost. The comet is not destroyed; instead, it splits into two chunks, one a mile and a half wide (named "Biederman") and the other six miles wide ("Wolf"), but both still world-threatening. Beck acknowledges Messiah’s failure, declares martial law, and announces that governments worldwide are building underground shelters. The United States' national refuge is in the limestone caves of Missouri. The US government conducts a lottery to select 800,000 ordinary Americans under 50 years of age, to join 200,000 pre-selected scientists, engineers, teachers, artists, soldiers, and officials. Lerner, Leo, and his family are pre-selected, but Leo's girlfriend Sarah Hotchner (Leelee Sobieski) is not. Leo marries Sarah to save her family but the Hotchners are mistakenly left off the evacuee list; Sarah refuses to leave without them.

A last-ditch effort to use Earth's missile-borne nuclear weapons to deflect the comets fails. Leo returns home looking for Sarah, but her family has left for the Appalachian Mountains on a jammed highway. Using the Hotchners' motorcycle, he catches up with them, and Sarah's parents insist that Leo take her and their infant daughter to high ground. Meanwhile, Lerner gives up her seat in an evacuation helicopter to her coworker Beth and her young daughter. The Biederman fragment impacts in the Atlantic Ocean near Bermuda. The resulting supersonic megatsunami quickly becomes hundreds of feet high as it heads inland. Leo and Sarah survive, but Lerner, Sarah's parents, and millions of others are killed along the Atlantic coasts of North America, South America, Europe, and Africa.

The world then braces for the impact of Wolf, which will strike western Canada and create a cloud of dust that will block out the sun for two years, killing all remaining plant, animal, and human life aside from those evacuated underground. Messiah—believed lost—reaches the fragment and enters a fissure to blow itself up. Messiah's suicide mission breaks up Wolf into much smaller pieces that burn up in Earth's atmosphere, sparing humanity.

The film closes with Beck speaking to a large crowd in front of the under-reconstruction United States Capitol, during which he urges the nation to continue its recovery.