She was born in Boulogne-Billancourt the daughter of actor Jean-Louis Trintignant and his second wife Nadine Marquand. When her younger sister died at the age of nine, Marie Trintignant became withdrawn and virtually stopped speaking. Throughout her early life she was afflicted by severe shyness, but despite this, by her mid-teens she had decided to become an actress.

She was the mother of four sons: Roman with drummer Richard Kolinka; Paul with actor François Cluzet; Léon with Mathias Othnin-Girard; and Jules with director Samuel Benchetrit.

Marie Trintignant died of a cerebral edema on August 1, 2003 while on a film location in Vilnius, Lithuania after being beaten up by her boyfriend Bertrand Cantat, lead singer for the French rock group Noir Désir. Her death caused considerable emotion in France. Bertrand Cantat was sentenced to 8 years in prison for manslaughter.

Marie Trintignant was nominated five times for France's most prestigious acting honor, the César Award for her roles in :

Comme elle respire - 1999 (best actress) Le cousin - 1998 (best supporting actress) Le cri de la soie - 1997 (best actress) Les Marmottes - 1994 (best supporting actress) Une affaire de femmes - 1989 (best supporting actress) She also appeared in the film noir Série noire of 1979.