Born and raised in La Goulette, a neighbourhood of Tunis, Cardinale won the "Most Beautiful Italian Girl in Tunisia" competition in 1957, the prize being a trip to Italy, which quickly led to film contracts, due above all to the involvement of Franco Cristaldi, who acted as her mentor for a number of years and later married her.

She went on to appear in the Hollywood films Blindfold (1965), Lost Command (1966), The Professionals (1966), Don't Make Waves (1967) with Tony Curtis, The Hell with Heroes (1968), and the Sergio Leone Western Once Upon a Time in the West (1968), a joint US-Italian production, in which she was praised for her role as a former prostitute opposite Jason Robards, Charles Bronson, and Henry Fonda.

Jaded with the Hollywood film industry and not wanting to become a cliché, Cardinale returned to Italian and French cinema, and garnered the David di Donatello for Best Actress award for her roles in Il giorno della civetta (1968) and as a prostitute alongside Alberto Sordi in A Girl in Australia (1971).

In 1974, Cardinale met director Pasquale Squitieri, who would become her partner, and she frequently featured in his films, including I guappi (1974), Corleone (1978), and Claretta (1984), the last of which won her the Nastro d'Argento Award for Best Actress.

In 2010, Cardinale received the Best Actress Award at the 47th Antalya "Golden Orange" International Film Festival for her performance as an elderly Italian woman who takes in a young Turkish exchange student in Signora Enrica.

[11] As a teenager, she was described as "silent, weird, and wild", and like other young women of her generation, was fascinated by Brigitte Bardot, who came to prominence in the 1956 film And God Created Woman, directed by Roger Vadim.

[16] She left at the end of her first term and decided to return home, earning herself a cover story in the popular weekly Epoca triggered by her unexpected decision to turn her back on a career as a film star.

[24] Under the new contract, in 1958, Cardinale was given a minor role with Italian actors Vittorio Gassman, Totò, Marcello Mastroianni, and Renato Salvatori in Mario Monicelli's internationally successful criminal comedy Big Deal on Madonna Street (I soliti ignoti).

[31] For seven years, Cardinale kept her secret, not only from the public, but also from her own son, Patrick, who grew up in the family with her parents and sister more or less as a brother[32] until the day Enzo Biagi, a journalist, discovered the truth.

[34] Cardinale also starred opposite Pietro Germi in his crime film The Facts of Murder, an important assignment for her in mastering the craft of acting while learning to feel at ease in front of the camera.

[57] She starred alongside Burt Lancaster in Visconti's The Leopard (1963) (Il Gattopardo), portraying a village girl who married a progressive young aristocrat (Alain Delon), and played a film actress cast by a director (Marcello Mastroianni) in Federico Fellini's 8½.

[58][59] She participated in the two films during exactly the same period, frequently moving from one to the other and experiencing the strictly planned approach of Visconti, which contrasted strongly with Fellini's much more relaxed style and his almost total reliance on improvisation.

[67] Cardinale acted in her first American film (although it was produced in Italy) when she played Princess Dala, a wealthy aristocratic woman who is the love and jewellery interest of David Niven in the Cortina d'Ampezzo-set The Pink Panther.

She also appeared alongside Rod Taylor in The Hell with Heroes and starred in one of her best-known roles as former prostitute Jill McBain in Sergio Leone's epic Western Once Upon a Time in the West.

"[87] In 1969, Cardinale starred opposite Nino Manfredi in Luigi Magni's Nell'anno del Signore, based on the actual story of the capital execution of two carbonari in papal Rome.

This was followed by a role as a telephone operator in Certo certissimo ... anzi probabile, and as a nurse opposite Sean Connery and Peter Finch in Mikhail Kalatozov's The Red Tent, based on the story of the mission to rescue Umberto Nobile and the other survivors of the crash of the Airship Italia.

[89] In 1971, she formed a duo with Brigitte Bardot in the French Western-comedy The Legend of Frenchie King, and appeared as a prostitute opposite Alberto Sordi in Luigi Zampa's comedy A Girl in Australia.

[93] In 1975, Cardinale played the daughter of a political exile (Adolfo Celi) in Mauro Bolognini's Libera, My Love, a character who becomes "increasingly incensed by the fascist government of Italy and makes a number of bold and very personal gestures against it".

[98] In 1978, Cardinale appeared in Damiano Damiani's political thriller, Goodbye & Amen – L'uomo della CIA, and again featured alongside Gemma in her husband's gangster picture, Corleone, set in 1950s Sicily.

[101] After a role in Si salvi chi vuole (1980), and a smaller part in Peter Zinner's The Salamander opposite Franco Nero, Anthony Quinn, and Christopher Lee,[102] Cardinale played the love interest of Marcello Mastroianni in Liliana Cavani's war picture The Skin, a film which also reunited her with Burt Lancaster.

The film was critically acclaimed, with Vincent Canby of The New York Times calling it "a fine, quirky, fascinating movie" and a "stunning spectacle", comparing the dynamic between Kinski and Cardinale to Katharine Hepburn and Humphrey Bogart in John Huston's The African Queen.

Made to celebrate the bicentennial anniversary of the French Revolution, the 360-minute Robert Enrico and Richard T. Heffron film was an international production, boasting a cast which included Klaus Maria Brandauer, Jane Seymour and Peter Ustinov.

[118] In 1993, Cardinale won the Leone d'oro alla carriera award at the Venice Film Festival, in which she was honoured along with Roman Polanski, Robert De Niro, and Steven Spielberg.

[120] In 1997, Cardinale featured in the British-Italian television drama miniseries Nostromo, directed by Alastair Reid and produced by Fernando Ghia of Pixit Productions, a co-production with Radiotelevisione Italiana, Televisión Española, and WGBH Boston.

[124] The following year, Cardinale played the peasant mother of two children who are members of Carmine Crocco's (Enrico Lo Verso's) army during the Garibaldi era, in Cristaldi's historical film Li chiamarono... briganti!.

She appeared as what Roger Ebert described as a "faded countess" opposite Jeremy Irons in Claude Lelouch's thriller film And Now... Ladies and Gentlemen,[127] portraying a character who spends her time in Fez, Morocco, with handsome gigolos.

[129] And Now... Ladies and Gentlemen received mixed reviews; A. O. Scott of The New York Times dismissed it as "sublimely silly", but praised the "impeccable CinemaScope compositions" and the "lush, suave score" by Michel Legrand.

[130] In 2007, Cardinale appeared in the Aline Issermann comedy film Cherche fiancé tous frais payés, opposite Alexandra Lamy and Bruno Salomone,[131] in a role which Patrick Besson described as "atrocious".

[132] After a role in the TV movie Hold-up à l'italienne (2008), the following year Cardinale starred in the critically acclaimed The String, playing a Tunisian mother who has a tempestuous relationship with her French-educated gay son.

He praised Cardinale's "terrific" acting and portrayal of the "overbearing" mother, likening one scene, where she "brings home a nice girl for Malik (Antonin Stahly) to meet", to Harold and Maude (1971).