Cassel first achieved recognition for his performance as a troubled Jewish youth in Mathieu Kassovitz's 1995 film La Haine (Hate) for which he received two César Award nominations.

[4] Cassel's breakthrough role was in Mathieu Kassovitz's critically acclaimed film La Haine (1995), in which he portrayed a troubled youth living in the deprived outskirts of Paris.

Other notable roles during this period of his career include the violent film Dobermann (1997), the genre-bending Brotherhood of the Wolf (2001), and the highly controversial Irréversible (2002), where he appears fully nude (with Monica Bellucci, after they married).

He has also dubbed the voice of Diego (Denis Leary) in the Ice Age franchise and Rodney Copperbottom (Ewan McGregor) in Robots.

In 2007, Cassel attracted significant critical acclaim for his performance in David Cronenberg's thriller film Eastern Promises, in which he starred opposite Viggo Mortensen and Naomi Watts.

Cassel appeared in a two-part film about Jacques Mesrine, who was France's "public enemy number one" in the seventies.

In 2011, Cassel played the lead role in the French-Spanish thriller-drama film The Monk, directed by Dominik Moll.

Screen Daily praised his performance, writing that "Cassel exudes otherworldly gravitas and his singular looks are perfect for the role.

[16] That year, he also attracted critical acclaim for his performance as Antoine in Xavier Dolan's It's Only the End of the World, which premiered at the Cannes Film Festival.

[18] In 2019, Cassel played the lead role in The Specials directed by Éric Toledano and Olivier Nakache based on the true story of Stephane Benhamou who ran an organization helping people with autism find employment and activities outside the confines of the institutionalized setting.

[19] In 2020, he portrayed trillionaire Engerrand Serac, the main antagonist of the third season of the HBO series Westworld.

[31][32] He married 21-year-old French model Tina Kunakey [fr] on 24 August 2018 in Bidart, France, after being in a relationship for more than two years.

[37] Besides his native French, Cassel speaks English, Portuguese, Italian, and basic conversational Russian, which he learned for his role in Eastern Promises.

[38] Cassel lived in Rio de Janeiro for five years, before moving back to Paris in 2018, and he used to have Brazilian citizenship.

[39][1] Cassel is known for having a great identification with Brazil, being a practitioner of the martial art of capoeira; he displayed this talent in the movie Ocean's Twelve.