She grew up in the La Croix-Rousse quarter of Lyon, France. This was an area with many Portuguese, Spanish and Italian immigrants. Her mother immigrated from Italy in the 1960s. Her French father left the family when Sylvie was just two years old.

In 1985, when she was 14, she saw Charlotte Gainsbourg in her role of the complex young girl in L'Effrontée, a film directed by Claude Miller, identified with Gainsbourg, and so took drama classes in Lyon with the actor and Director Christian Taponard. In 1989, she moved to Paris and spent three years at the Conservatoire (CNSAD). In the early and mid 1990s, she landed her first small roles in films like L'Histoire du garcon qui voulait qu'on l'embrasse, directed by Philippe Harel, and Love, etc., directed by Marion Vernoux. In 1997 she had great success in Germany with Caroline Link's Jenseits der Stille for which she learned German, sign language, and the clarinet. In 1998 she had her first major role in French cinema playing Béa in Thomas Vincent's Karnaval. In 2000 she starred in Chantal Akerman's La Captive, an adaptation of La Prisonièrre, the fifth part of Marcel Proust's A La Recherche du Temps Perdu. In 2001 she won the César Award for Most Promising Actress for her portrayal of Christine Papin, one of the Papin sisters, in Les Blessures assassines (English title: Murderous Maids). The story concerned a young servant woman found guilty of the murder, with her sister's help, of her employer's wife and daughter; it had made sensational headlines in France in 1933.

In 2003, she published the autobiographical book Il n'y a pas beaucoup d'étoiles ce soir, with anecdotes of her day-to-day life as an Actress. The French edition featured a cover designed by her sister Ghislaine.

One of her most noted performances was as the star of the film Stupeur et tremblements, adapted from the novel by Amélie Nothomb, for which she was awarded a César and a Lumières Award for Best Actress in 2004. She plays a woman struggling with the difference in culture between the Japanese Business world and the western, Belgian world, from which she comes. In 2005 or 2006 she returned to her native Lyon (to the Théâtre de la Croix Rousse), where she played the rôle of Edith in Philippe Faure's adaptation of Stefan Zweig's La Pitié dangereuse. She starred in 2007's two-time Academy Award-winning film La Vie en Rose, as Momone, Edith Piaf's best friend. In the 2008 film Sagan, she portrayed the Writer Françoise Sagan, earning unanimous praise for her hauntingly accurate portrayal and for which she was again nominated for the César for best Actress.

She has a son, Ruben, born on 15 February 2005, and a daughter Esther, born in January 2011.

She was made Chevalier (Knight) of the Ordre national du Mérite in March 2009.

In 2012, she participated in Rendez-vous en terre inconnue.