The story begins with Arthur having his house destroyed by a construction crew to make way for a bypass. Shortly after he finds out from Ford that the Earth itself would soon meet the same fate at the Hands of a Vogon construction crew. Ford reveals to Arthur that he is not an out of work actor, but rather an alien from somewhere in the vicinity of Betelgeuse. They hitch a ride on one of the Vogon ships to make their escape.

Unfortunately hitching a ride is against Vogon regulations, and the stowaways are caught, subjected to Vogon poetry (widely accepted as the third worst poetry in the universe) and tossed into space. Fortunately they are rescued by the Heart of Gold a ship powered by an infinite improbability drive. The ship was stolen by Zaphod Beeblebrox, the President of the Galaxy. Also on board are Marvin, a robot suffering from depression, and Trillian, a human female mathematician and astrophysicist that Arthur had once met at a party.

They wind up on the planet Megarathea, where luxury planets were manufactured. It is revealed that the Earth was a supercomputer constructed to find the question to the answer to the life, the universe, and everything by a race of hyper-intelligent pan-dimensional beings. Unfortunately 10 million years later, and five minutes before the program had run to completion, the Earth was destroyed by Vogons. Two of the beings, which had stowed away on the Heart of Gold as mice, recognized that Arthur as a last generation human had the question imprinted in his brains. They offered to buy his brains from him, but he objected, resulting in a fight. A diversion is created when the galactic police show up to arrest Zaphod for stealing the Heart of Gold. The galactic police die when their life support fails, allowing the Arthur and his companions to escape. The group then decides to travel to The Restaurant at the End of the Universe for lunch.