Born Greta Gracco in Milan, Italy, the daughter of Luca Scacchi Gracco, an Italian art dealer and painter, and Pamela Carsaniga, an English-born dancer and antiques dealer. Her parents divorced when she was three, and her mother moved to England with her and her two older brothers. In 1975, following her mother's remarriage to Giovanni Carsinga, the family moved to Adelaide, Australia.

In 1977, Scacchi returned to England to pursue an acting career. She studied at the Bristol Old Vic Theatre School, with Miranda Richardson and Amanda Redman. In 1982, she made her film debut in the German movie Das Zweite Gesicht (The Second Face) and gave versatile performances in films such as Heat and Dust (1983), The Ebony Tower (1984), White Mischief (1987), Presumed Innocent (1990), The Player (1993) and Country Life (1994).

She has appeared nude, including frontal nudity, in several films. According to New Idea magazine, she has appeared naked in more films than any other "Australian" actress. She turned down the role of Catherine Trammell in Basic Instinct (1992).

In 1996 she won an Emmy Award for her work as Empress Alexandra Fyodorovna of Russia in the television film Rasputin: Dark Servant of Destiny. She was nominated for a Golden Globe and numerous other awards. In 2007 she received another Emmy Award nomination for Supporting Actress In A Miniseries Or A Movie for Broken Trail.

She speaks French, German and Italian fluently, which has made her a popular choice for the casting directors of European films and has been an asset when working for European directors and producers.