Cassel was born on 23 November 1966 in Paris, France, to Sabine Litique, and French actor Jean-Pierre Cassel (born Jean-Pierre Crochon). Cassel's brother, Mathias, is a rapper with the group Assassin under the name "Rockin' Squat". His half-sister, Cécile Cassel, is an actress.
Cassel's breakthrough role was in Mathieu Kassovitz's critically acclaimed film La Haine where he played a troubled youth from the deprived outskirts of Paris. He has gone on to act in a variety of films such as the moody L'Appartement (with Monica Bellucci before they married), the violent Dobermann, the genre-bending Le Pacte des Loups (in English, Brotherhood of the Wolf), and the highly controversial Irréversible, where he appears fully nude (with Monica Bellucci after they married).
Cassel has also appeared in a number of English-language films, such as Ocean's Twelve and Ocean's Thirteen, Derailed, Birthday Girl, The Messenger: The Story of Joan of Arc, Elizabeth, Eastern Promises, and Shrek (as the voice of Monsieur Hood), and in the Portuguese-language, Brazilian film Adrift (À Deriva). In 2006, he appeared in Sheitan, in which he played a shepherd who carries out satanic rituals. In 2008, he appeared in two movies about Jacques Mesrine, who was France's "public enemy number one" in the seventies. Cassel received the 2009 Cesar award for best actor for his performance in Mesrine directed by Jean-Francois Richet.
An early appearance on British television was as Nicole's boyfriend in the 1994 Renault Clio advert which was used in the UK.
In October 2008, Cassel was signed to be the face of a new Yves Saint Laurent men's fragrance. The new fragrance, La Nuit de l'Homme, was launched worldwide in March 2009.
French film historian Tim Palmer describes Cassel as one of the most charismatic and idiosyncratic of all France's contemporary stars, working in both popular and more intellectual modes of cinema, typically playing characters that veer unpredictably between positive/alluring and negative/grotesque—often, in fact, within a single role and performance.
In 2009, he made his debut as a singer on Zap Mama's album ReCreation, singing alongside them on the singles "Paroles, Paroles" and "Non, Non, Non".
He played Thomas Leroy in Darren Aronofsky's critically acclaimed Black Swan (2010), alongside Natalie Portman and Mila Kunis. He will play Zumi in Rupert Sanders's samurai adventure fantasy film The Lost Sea Horizon, opposite Sandra Bullock and Fan Bingbing.
Cassel met Italian actress Monica Bellucci on the set of their 1996 film The Apartment. They married in 1999, and have two daughters, Deva (born 12 September 2004) and Léonie (born 21 May 2010). Cassel and Bellucci announced their divorce on 26 August 2013.
Cassel has a passion for the martial art of capoeira and displayed his talent in the movie Ocean's Twelve. He also trains in wing chun.
Since 2013, Cassel lives in Rio de Janeiro, initially in Arpoador (with ex-wife Monica Bellucci) and after their divorce, in Morro do Vidigal. He is known for having great identification with Brazil, being a specialist in capoeira.
Besides his native French, Cassel speaks English, Portuguese, Italian and basic conversational Russian which he learned for his role in Eastern Promises.