- Dennis Quaid as Professor Jack Hall, government climatologist and father of Sam Hall.
- Jake Gyllenhaal as Sam Hall, teenage son of Jack and Lucy Hall.
- Emmy Rossum as Laura Chapman, love interest and classmate of Sam Hall.
- Ian Holm as Professor Terry Rapson, colleague of Jack Hall stationed in Scotland.
- Christopher Britton as Vorsteen, associate of Jack.
- Arjay Smith as Brian Parks, best friend and classmate of Sam Hall.
- Dash Mihok as Jason Evans, friend and colleague of Jack.
- Jay O. Sanders as Frank Harris, friend and colleague of Jack.
- Sasha Roiz as Parker, an astronaut aboard the International Space Station.
- Sela Ward as Dr. Lucy Hall, physician/doctor, wife of Jack and mother of Sam.
- Austin Nichols as J.D., rival turned friend of Sam.
- Adrian Lester as Simon, colleague and friend of Terry Rapson.
- Tamlyn Tomita as Janet Tokada, Hurricane specialist for NASA, colleague of Jack Hall.
- Glenn Plummer as Luther, a homeless man in NYC.
- Perry King as President Blake, President of the United States.
- Kenneth Welsh as Raymond Becker, Vice President of the United States, later President of the United States.
- Amy Sloan as Elsa, a woman who remains in the library and survives with the group.
- Sheila McCarthy as Judith, the librarian.
- Nestor Serrano as Gomez, director of NOAA.
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