Born in Maisons-Laffitte, Seine-et-Oise (now Yvelines), near Paris, he studied art at high school until he graduated in 1982. Chomet moved to London in 1988 to work as an Animator at the Richard Purdum studio. In September of that year, he established a freelance practice, working on commercials for clients such as Principality, Renault, Swinton and Swissair.

In addition to his animation career, Chomet created many print comics, starting in 1986 with Secrets of the Dragonfly. In 1992 Chomet wrote the script for a science fiction comic called The Bridge in Mud. 1993 saw Chomet writing the story for Léon-la-Came, which was drawn by Nicolas de Crécy for À Suivre magazine. This was published in 1995 and won the René Goscinny Prize in 1996. In 1997, Chomet published Ugly, Poor, and Sick, again with Nicolas de Crécy. This won them the Alph-Art Best Comic Prize at the Angoulême Comics Festival.

In 1991, Chomet started work on his first animated film, The Old Lady and the Pigeons (La Vieille Dame et les pigeons), with backgrounds designed by de Crécy. In 1993, Chomet moved to Canada. During 1995 and 1996, he finished work on The Old Lady and the Pigeons. The short film won him a BAFTA, the Grand Prize at the 1997 Annecy International Animated Film Festival, the Cartoon d'or prize, as well as the Audience Prize and Jury Prize at the Angers Premiers Plans Festival. It also received an Oscar nomination for best animated short film.

Upon the release of The Triplets of Belleville, Nicolas de Crécy accused Chomet of plagiarising his work, citing it as the reason for the dissolution of their collaboration. The visual style of The Triplets of Belleville closely resembles the earlier work of Nicolas de Crécy's 1994 graphic novel Le Bibendum Céleste.

In the mid-2000s Chomet founded an animation studio in Edinburgh, Scotland, called Django Films. The Django Films studio was set up with the ambition to produce a number of films and establish itself in the film-making scene in both animation and live action but now is being dismantled. In its life span Django was beset with production difficulties, first losing funding for what was to be its first animated feature, Barbacoa, failing to secure funding for what was labelled "A Scottish Simpsons" for the BBC then came the very public sacking of Chomet as Director from The Tale of Despereaux by Gary Ross. Django Films never got close to employing the 250 artists that it would require, as reported by Scotland on Sunday in 2005. Chomet has been critical of the standard of British art schools in their lack of ability to produce sufficiently skilled animators required for his Edinburgh Studio.

Chomet's first feature-length animated film, The Triplets of Belleville (Les Triplettes de Belleville, or Belleville Rendez-vous in the UK) was also nominated for two Oscars in 2003 (Best Animated Feature and Best Song), and introduced Chomet's name to a much wider audience.

In 2005 he directed a segment for the collaborative film Paris, je t'aime; he was assigned the 7th arrondissement (the Eiffel Tower). It was Chomet's first work in live action.

According to the 2006 reading of The Illusionist script at the London Film School introduced by Chomet, "The great French comic Jacques Tati wrote the script of The Illusionist and intended to make it as a live action film with his daughter."

Chomet's next film was The Illusionist (L'Illusionniste), which premiered at the 60th Berlin International Film Festival in February 2010, after many delays (it was first planned for release in 2007). The Illusionist, like Chomet's previous work, has its roots in mid twentieth century popular French culture. It is based on an unproduced script that Jacques Tati had written in 1956 as a personal letter to his estranged eldest daughter, and stars an animated version of Tati himself. It was originally conceived by Tati as a journey of love and discovery that takes two characters across western Europe to Prague. Chomet says that "Tati wanted to move from purely visual comedy and try an emotionally deeper story" and states that "It's not a romance, it's more the relationship between a dad and a daughter". It cost an estimated £10 million to make, and was funded by Pathé Pictures.

In 2014, a couch gag directed by Chomet aired for an episode of The Simpsons. The weekly entertainment-trade magazine Variety also announced that Chomet was moving forward with the project, The Thousand Miles, a mix of live action and animation based on various works of Federico Fellini including his "unpublished drawings and writings" with a screenplay by Demian Gregory and Tommaso Rossellini.

In 2015, Chomet directed and co-wrote the animated music video 'Carmen' for Belgian musician Stromae.