Gondry was born in Versailles, France. His career as a filmmaker began with creating music videos for the French rock band Oui Oui, where he also served as a drummer. The style of his videos caught the attention of music artist Björk, who asked him to direct the video for her song "Human Behavior". The collaboration proved long-lasting, with Gondry directing a total of six music videos for Björk. Other artists who have collaborated with Gondry on more than one occasion include The White Stripes, The Chemical Brothers, and Kylie Minogue. Gondry has also created numerous television commercials; one of his most famous ones, for Levi's jeans, won the Lion D'or at the Cannes Film Festival. He pioneered the "bullet time" techniques used in The Matrix, notably in his "Like A Rolling Stone" video for the Rolling Stones and a 1998 commercial for Smirnoff vodka, as well as directing a trio of inventive holiday-themed commercials for The Gap.

Gondry is often cited, along with directors Spike Jonze and David Fincher, as representative of the influx of music video directors into feature film. Gondry made his feature film debut in 2001 with Human Nature, garnering mixed reviews. His second film, Eternal Sunshine of the Spotless Mind (also his second collaboration with screenwriter Charlie Kaufman), was released in 2004 and received numerous rave reviews. Eternal Sunshine utilizes many of the image manipulation techniques that Gondry had experimented with in his music videos. Gondry won an Academy Award alongside Kaufman and Pierre Bismuth for the story of Eternal Sunshine.

His brother Olivier 'Twist' Gondry is also a television commercial and music video director creating videos for bands such as The Stills, Hot Hot Heat, The White Stripes and The Vines.