Arthur Dent (MARTIN FREEMAN) is an ordinary, unassuming man who's shocked one morning to discover that his house is slated for demolition to make way for a highway bypass. His best friend, Ford Prefect (MOS DEF), informs him that's the least of his worries. It seems that an alien race known as the Vogons have scheduled Earth to be demolished to make way for a hyperspace expressway. With only minutes to go, Ford -- with Arthur in tow -- manages to hitch a ride on the Vogon spaceship and thus avoids the total destruction of Earth.
With the aide of the interactive "The Hitchhiker's Guide to the Galaxy" -- that gives the advice "don't panic" -- the two try to figure out what's going on. Unfortunately, they're captured by the Vogons and then cast off into space by their leader, Prostetnic Vogon Jeltz (voice of RICHARD GRIFFITHS), but are then picked up by the spaceship The Heart of Gold.
Inside are Zaphod Beeblebrox (SAM ROCKWELL), the zany, two-headed President of the galaxy; his girlfriend Trillian (ZOOEY DESCHANEL) who earlier met Arthur at a costume party when she was known as Tricia on Earth; and Marvin (voice of ALAN RICKMAN), a chronically depressed robot.
Zaphod is in search of the meaning of life and the universe and thus seeks answers from the all-knowing super computer Deep Thought (voice of HELEN MIRREN). On their way, however, they must contend with repeated run-ins with the Vogons as well as religious leader and former Zaphod opponent Humma Kavula (JOHN MALKOVICH), and an encounter with Slartibartfast (BILL NIGHY) who knows a thing or two about Earth.