Farmiga, the second oldest of seven children, was born in Passaic County, New Jersey to Michael and Luba Farmiga, Ukrainian immigrants. She was raised in an insular Ukrainian American community, not speaking English until the age of six. During her teen years, she attended a Ukrainian Catholic school and toured with a Ukrainian folk-dancing company.

Although she originally intended to become an optometrist, Farmiga attended Syracuse University's School of Visual and Performing Arts. She made her Broadway debut in 1996, as an understudy in the play Taking Sides. The same year, she starred as "Miranda" in the American Conservatory Theater production of The Tempest. Throughout the late 1990s, she continued appearing in both stage, television and film roles, including a part in the 1998 film, Return to Paradise.

Farmiga appeared in several high profile films in the early 2000s, including Autumn in New York and 15 Minutes. Her lead performance in the 2005 independent film, Down to the Bone, received a "Best Actress" award from the Los Angeles Film Critics Association. Farmiga subsequently co-starred with Paul Walker in the 2006 action-thriller, Running Scared.

Farmiga is married to actor Sebastian Roache, who co-starred with her in the television series, Roar. The two eloped to the Bahamas after the series' end.