Bellucci was born in Città di Castello, Umbria, Italy, the daughter of Maria Gustinelli, a painter, and Luigi Bellucci, who owned a trucking company. Bellucci started modelling at 16, when she was attending the Liceo classico. Initially pursuing a career as a lawyer, Bellucci modeled to pay her tuition at the University of Perugia, but the lifestyle tempted her away from her law studies. She speaks Italian, French, and English fluently, Spanish semi-fluently, and she has had speaking roles in each of these languages as well as in Aramaic for her part as Mary Magdalene in The Passion of the Christ.
Bellucci is married to fellow actor Vincent Cassel, with whom she has appeared in several films, and has a daughter named Deva (born 12 September 2004). In 2004, while pregnant with her daughter, Bellucci posed nude for the Italian Vanity Fair Magazine in protest against Italian laws that prevent the use of donor sperm.
In 1988, Bellucci moved to one of Europe's fashion centers, Milan, where she signed with Elite Model Management. By 1989, she was becoming prominent as a fashion model in Paris and across the Atlantic, in New York City. She posed for Dolce & Gabbana and French ELLE, among others. In that year, Bellucci made the transition to acting and began taking acting classes. The February 2001 Esquire Magazine's feature on Desire featured Ms. Bellucci on the cover and in an article on the five senses. In 2003, she was featured in Maxim. In 2004, she topped AskMen's 100 Most Beautiful Women in the World annual list. Bellucci's modelling career is managed by Elite+ in NYC. She is considered an Italian sex symbol. She is currently a face of a range of Dior Cosmetics. Bellucci is also signed to Storm Model Management in London.
Bellucci's film career began in the early 1990s. In 1992, she made her first appearance in a major English-language film as one of Dracula's brides in Bram Stoker's Dracula. She became known and popular with worldwide audiences following her roles in Malèna, Brotherhood of the Wolf and Irréversible, though is perhaps best known for her role as Persephone in The Matrix Reloaded and The Matrix Revolutions followed by her portrayal of Mary Magdelene in The Passion of the Christ.
In a documentary about the film, The Big Question, she stated: "I am an agnostic, even though I respect and am interested in all religions. If there's something I believe in, it's a mysterious energy; the one that fills the oceans during tides, the one that unites nature and beings."
In 2003, Bellucci starred in Tears of the Sun as a doctor in Nigeria being rescued by the U.S., and in 2005 in the fantasy film The Brothers Grimm as a beautiful evil queen. Her latest films are The Stone Council, directed by the Frenchman Guillaume Nicloux (2006) and Manuale d'amore 2 (2007) where she portrays a physiotherapist who is the object of the desire of her patient. She was supposed to be seen portraying Indian politician Sonia Gandhi in the biopic Sonia, originally planned for release in 2007 but now shelved. September 2007 saw the release of Shoot 'Em Up, where she plays a prostitute opposite Clive Owen. She dubbed her own voice for the French and Italian releases of the film.
She filmed Le Deuxième souffle with Daniel Auteuil, Michel Blanc and Eric Cantona (2006).
Bellucci also voiced Kaileena in the video game Prince of Persia: Warrior Within, and the French voice of Cappy for the French version of the 2005 animated movie Robots.
In 2007, she appeared in Heartango, a movie for Intimissimi, with José Fidalgo and directed by Gabriele Muccino.
In 2003, Bellucci won the Nastro d'Argento Best Supporting Actress award for her portrayal of Alessia in Remember Me, My Love. She has been nominated for several others, including the 1996 César Award for Best Supporting Actress for her portrayal of Lisa in L'Appartement.