While studying at Business school, he trained as an actor, somewhat against his will; his first stage role was in a play called Sur une plage de l'Ouest (On a beach in the West). After graduation, he enrolled in drama classes with Tania Balachova and then met Daniel, a Director under whose auspices he worked from 1974 to 1981, participating in a dozen productions, mainly of contemporary classics.

Berléand began his film career in 1978 with supporting roles in successful comedies throughout the 1980s. After a series of highly acclaimed supporting roles, including My Small Business for which he won the César for best actor in a supporting role in 2000, he won his first major role in the film My Idol by Guillaume Canet which brought his name and face to the wider public. For this, Berléand thanks his former girlfriend, actress-director Nicole Garcia.

In Martin et Léa, he plays a police inspector, a role he went on to perform many times on screen (La Balance, Les mois d'avril sont meurtriers (April is a Murderous Month, based on the novel by Derek Raymond), Marche à l'ombre (Walking in the Shade), The Bait, The Death the Chinese, Fred, The Smile of the Clown, Ne le dis à personne (Tell No One), Transporter 1, 2, and 3) thanks in part to a cold, distant, and a piercing gaze. Berléand often plays military characters (The Hostage of Europe, Stella, Les Milles, Captain Conan, The Prince of the Pacific); he has also played a detective (Follow This Plane), pastor (Au revoir les enfants) and Psychiatrist in Seventh Heaven, the film that really showed his talents to the public in late 1997.

He plays Gilles Triquet, the officer manager and equivalent of David Brent in Le Bureau, the French version of The Office, produced by Canal+. He released a book about his childhood in 2006, Le fils de l'homme invisible (The son of the invisible man). He also appeared in the 2002 film The Transporter as the French commissaire named Tarconi, an active and honest police officer who is an acquaintance of Frank Martin (Jason Statham). He reprised the role in the sequels Transporter 2 and Transporter 3 and the TV series.

Berléand has been in a long-term relationship with Alexia Stresi; their twins Adèle and Lucy were born in December 2008. He is also the father of two grown children aged 26 and 31 years.