Schreiber starred in Jonathan Demme's The Manchurian Candidate, playing Raymond Shaw, the son of the powerful Senator Eleanor Prentiss Shaw (Meryl Streep), and a decorated Gulf War hero who becomes a candidate for vice president of the United States.

Schreiber's other credits include The Sum of All Fears, Kate and Leopold, Hamlet, The Hurricane, A Walk on the Moon, Twilight, Sphere, Scream, Scream II, Scream III, Mixed Nuts, and Ransom.

Schreiber is also known for his work in such acclaimed independent features as 'The Daytrippers, Big Night, Party Girl, Walking and Talking, Mad Love, Denise Calls Up and Spring Forward, for which he also served as a producer.

Although initially interested in playwriting, Schreiber spent a year studying acting with the faculty from England's Royal Academy of Dramatic Arts. In 1992, he graduated with an MFA from the Yale School of Drama. Schreiber's stage credits include a critically acclaimed turn as Henry V in a Shakespeare in the Park production at the Delacorte Theatre; The Mercy Seat, opposite Sigourney Weaver and directed by Neil Labute; Harold Pinter's Betrayal, co-starring Juliette Binoche; and Moonlight with Blythe Danner and Jason Robards.

Schreiber's enduring relationship with the Public Theatre's New York Shakespeare Festival has produced several critically acclaimed performances including the title role in Hamlet, Iago in Othello, Macbeth, The Tempest, and Cymbeline, for which he won an Obie award.

For television, Schreiber starred as Orson Wells in RKO 281 (receiving Emmy and Golden Globe nominations) and in Lackawana Blues with Halle Berry, Jeffrey Wright and Rosie Perez.