She was one of the biggest stars of Italian film during the Fascist era, once being called "the most beautiful woman in the world" by Benito Mussolini, and was internationally successful post-World War II.

Valli worked with many significant directors both in Italy and abroad, including Alfred Hitchcock (The Paradine Case; 1947), Carol Reed (The Third Man; 1949), Luchino Visconti (Senso; 1954), Michelangelo Antonioni (Il Grido; 1957), Georges Franju (Eyes Without a Face; 1960), Pier Paolo Pasolini (Oedipus Rex; 1967), Mario Bava (Lisa and the Devil; 1972), Bernardo Bertolucci (1900, 1976; La Luna; 1979), and Dario Argento (Suspiria; 1977).

Intellectually gifted, at fifteen Valli travelled to Rome, where she attended the Centro Sperimentale di Cinematografia, the oldest school for film actors and directors in Western Europe and still one of the most prestigious.

Valli started her movie career in 1934, in Il cappello a tre punte (The Three Cornered Hat) during the so-called Telefoni Bianchi cinema era.

During the Second World War, she starred in many movies, including Stasera niente di nuovo (1942) (whose song "Ma l'amore no" became the leitmotif of the Italian forties) and the diptych Noi Vivi / Addio Kira!

By her early 20s, already widely regarded as the "most beautiful woman in the World", Valli had a career in English-language films through David Selznick, who signed her a contract, thinking that he had found a second Ingrid Bergman.

In Hollywood, she performed in great successes and memorable movies, in Alfred Hitchcock's The Paradine Case (1947) with Gregory Peck; with Fred MacMurray and Frank Sinatra (in his first non-musical performance), in The Miracle of the Bells (1948); alongside Orson Welles and Joseph Cotten in Carol Reed's The Third Man (1949), regarded as one of the best movies ever made worldwide and the British Film Institute selection as the greatest British film of all time; and again with Cotten in Walk Softly, Stranger (1950).

"[5] The actress could not tolerate the strict rules of Selznick, who imposed total control on his actors, and managed to gain her contract's rescission, though with the payment of a high penalty.

From the 1960s, she worked in several pictures with prominent directors, such as Pier Paolo Pasolini's Edipo re (Oedipus Rex), 1967; Bernardo Bertolucci's La strategia del ragno, 1972; Novecento, 1976, and Dario Argento's Suspiria, 1977.

In Italy, she was also well known for her stage appearances in such plays as Ibsen's Rosmersholm; Pirandello's Henry IV; John Osborne's Epitaph for George Dillon; and Arthur Miller's A View from the Bridge.

Among the accused – all of whom were acquitted, leaving the case unsolved – was Valli's lover, jazz musician Piero Piccioni (son of the Italian Minister of Foreign Affairs).