He got his first acting job in 1976 when the producers of Sinbad and the Eye of the Tiger discovered Mayhew from a photograph in a newspaper article about men with large feet, and they cast him in the role of the minotaur.
When casting roles for his first Star Wars film, producer George Lucas needed a tall actor who could fit the role of the beastly Chewbacca. He originally had in mind 6 feet 6 inches (1.98 m) bodybuilder David Prowse, but he was instead cast to play Darth Vader. This led Lucas on a search which turned up Mayhew, who says that all he had to do to be cast in the role of Chewbacca was stand up. He reprised his signature role during Star Wars Episode III: Revenge of the Sith, which was released in cinemas on his birthday in 2005.
Mayhew has played the part of Chewbacca in four Star Wars films: the original Star Wars trilogy (Star Wars Episode IV: A New Hope, Star Wars Episode V: The Empire Strikes Back, and Star Wars Episode VI: Return of the Jedi), and Star Wars Episode III: Revenge of the Sith. He also played the role in the 1978 television film The Star Wars Holiday Special, as well as in an appearance on The Muppet Show. and Mickey's 50 addition, he recorded dialogue as Chewbacca for the animated show The Clone Wars, in the Season 3 finale episode called Wookiee Hunt.
Mayhew also plays the role in commercials and for hospital appearances for sick children. When cast in the role, he studied the movement of large animals at the zoo to come up with an authentic sense of movement for Chewbacca. When Mayhew grew ill in the shooting of The Empire Strikes Back, a similarly tall stand in was used, but the actor could not match Mayhew's studied movement style and the scenes had to be re-shot upon Mayhew's recovery. Mayhew did not provide the voice of Chewbacca; that was created by the film's sound designer, Ben Burtt, by mixing together the growls of different animals.
Mayhew has made numerous appearances as Chewbacca outside the Star Wars films. Mayhew as Chewbacca was honoured with a Lifetime Achievement Award at the MTV Film Awards 1997. He was additionally honoured at the release of the new PlayStation Portable where he dressed as Chewbacca and held up the new PSP slim version.
He has made other media appearances without the Chewbacca costume. Mayhew appeared on NBC's Identity, where his identity was based on the fact that he played Chewbacca.
Mayhew commented at a mid-1990s Sci-Fi convention on his experience on The Muppet Show, saying, "Doing The Muppet Show you forget about conventional filming." In his appearance with the Muppets, Mayhew was required to dance as Chewbacca during the closing number. Mayhew dubbed the dance the "Wookie Waltz", and admits: "I have got two left feet."
In addition to his role as Chewbacca, he also played himself in Comic Book: The Movie.