In 1992, Klapisch shot his first feature film, Riens du tout. A year later, a TV channel asked him to make a film about high school life, set in 1975, Le péril jeune. The film had a very small budget and featured Romain Duris and Vincent Elbaz, who would become two of his favourite actors. Due to its success when broadcast on TV, the film was released in the theaters two years later. During the 1990s, Klapisch made three short films to encourage the use of condoms in combatting AIDS: La chambre, Le Poisson Rouge and Le Ramoneur des Lilas.
Klapisch's next film, Ni pour, ni contre (bien au contraire), had its production delayed for 4 months. During this period, he devised a new, low-budget product, which became L'Auberge Espagnole (The Spanish Apartment). Shot in Spain, this film became his greatest box-office success. In 2005, he filmed a sequel to L'Auberge Espagnole, Les Poupées Russes (Russian Dolls), with many of the same actors from L'Auberge Espagnole. His film Paris was released in February 2008, and Ma part du gâteau in 2011. In 2012, Klapisch filmed Casse-tête chinois (Chinese Puzzle). This sequel to Les Poupées Russes was released in 2013.