Mary Elizabeth Mastrantonio was born to Mary D. (Pagone) and Frank A. Mastrantonio, who owned a bronze foundry, in Lombard, Illinois, with her parents being of Italian descent. She was raised in Oak Park, Illinois, and began her acting career in school plays as a teenager.
Mastrantonio attended the University of Illinois and got bitten by the acting bug, starring in "Guys and Dolls". She then left for New York, where she took part in "West Side Story" in 1981. Her breakthrough in movies came with her starring role alongside Al Pacino in Scarface (1983).
In 1985, she starred in The Color of Money (1986),which earned her an Academy Award nomination for Best Supporting Actress. Around 1990, a string of movies brought her significant attention, including important roles in The Abyss (1989),Class Action (1991),and Robin Hood: Prince of Thieves (1991).
During this time, she married director Pat O'Connor, who directed her in The January Man (1989). Mastrantonio is also a renowned cabaret-style singer, and her singing is showcased in John Sayles's Limbo (1999).
In her later career, Mastrantonio decided to choose roles she liked rather than those that would attract attention. She also took time off to be with her family. As of 2001, she lives with her husband and two children in London, England, UK.