Fenech was born in Bône (now Annaba), in French Algeria to a Maltese father and Sicilian mother. From the late 1960s to early 1980s, Fenech starred in many types of European movies. She is best known for her erotic comedies, and began to work in that field in the late 1960s with Austrian director Franz Antel. Fenech also achieved fame with giallo and sex films such as Five Dolls for an August Moon, Your Vice Is a Locked Room and Only I Have the Key and Sex with a Smile, many of which were directed by Sergio Martino.

In the 1980s, she became a television personality, typically appearing with Barbara Bouchet on a chat show on Italian television. In the mid-1990s, she was engaged to the well-known Italian industrialist Luca di Montezemolo.

After many years of work in movie production (she produced, among others, The Merchant of Venice, 2004, with Al Pacino), Fenech accepted Quentin Tarantino's offer to star in another movie, Hostel: Part II (2007), directed by Eli Roth. A British general named Ed Fenech (played by Mike Myers) is a character in Tarantino's 2009 film Inglourious Basterds.

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