Before appearing in The Godfather in 1972, Stefanelli had small supporting roles in numerous Italian films directed by renowned Italian Directors — La moglie giapponese (The Japanese Wife) by Gian Luigi Polidoro, Non commettere atti impuri (Do Not Commit Adultery) by Giulio Petroni, Homo Eroticus by Marco Vicario and In nome del popolo italiano (In the Name of the Italian People) by Dino Risi. In 1972, she appeared in German television film Die Sonne angreifen (To Attack the Sun) by Peter Lilienthal. The same year, she landed the role of Apollonia Vitelli-Corleone in American crime film The Godfather, directed by Francis Ford Coppola and starring Marlon Brando, Al Pacino, Robert Duvall, James Caan and Diane Keaton. Although she was only sixteen when the production began, and only seventeen when the film came out, her character was featured in the 1977 miniseries The Godfather: A Novel for Television.

Stefanelli was married to the actor/director Michele Placido, with whom she appeared in a number of films, including the 1975 erotic drama Peccati in famiglia. They had three children together, including Actress Violante Placido, and they divorced in 1994. Following their divorce, Stefanelli and her children briefly lived in London.

Having quit her acting career in 1992, Stefanelli now owns and operates a fashion store in Rome called Simo Bloom, where she designs purses and shoes.

Stefanelli refused a career in Hollywood, in order to avoid being typecast. She explained during an interview in 1997 about the offers of Hollywood filmmakers: "They wanted nothing more than to expose my body...I refused so much work." She continued her career in Italy. In 1973, she filmed one picture in Spanish, El mejor alcalde, el rey (The Best Mayor, the King), directed by Rafael Gil. The following year, Stefanelli appeared in the miniseries Moses the Lawgiver, starring Burt Lancaster, Anthony Quayle and Ingrid Thulin. She would later have roles in numerous Italian films, including Peccati in famiglia (Scandal in the Family), an erotic drama she starred opposite her husband Michele Placido, and Francesco Rosi's Tre fratelli (Three Brothers). Eriprando Visconti, Walerian Borowczyk, Franco Castellano, Giuseppe Moccia and Mario Caiano are some of the Directors she worked with. After appearing in Michele Placido's film Le amiche del cuore (Close Friends), Stefanelli ended her acting career in 1992, just one year before her daughter Violante Placido began her acting career.

A hoax stating that Stefanelli had died appeared on the Internet in 2006, and then again in 2008.

If a film project came along, she might take it, Stefanelli said. “But after my death, I don’t know,” she laughed.