Miller is multiracial, being of African American, Jamaican, English, and German Jewish descent on his father's side, and of Russian, French, Dutch, Syrian and Lebanese descent on his mother's. He was born in Chipping Norton, Oxfordshire, England where his father, a Rhodes Scholar, was studying. Miller was raised in Brooklyn, New York after his family moved back to the United States. After graduating from Quaker Valley Senior High School, Miller attended Princeton University. He graduated in 1995 with a degree in English, and travelled the world performing with the school's famed a capella group, The Princeton Tigertones. Subsequently, Miller headed to Los Angeles, California to pursue an acting career. Miller ended up spending years doing behind-the-scenes work to support himself before devoting himself seriously to auditioning for acting roles.

Miller's first starring role was as the sensitive and introverted David in ABC's mini-series Dinotopia. After appearing in a few minor television roles, Miller moved on to co-star in the film The Human Stain (2003), playing the younger version of an African American character who decides to pass for white played by Anthony Hopkins. Miller further increased his profile in 2005 when he starred in singer Mariah Carey's music videos, "It's Like That" and "We Belong Together." He currently has a main role as Michael Scofield in the successful Fox Network television drama Prison Break, for which he received a 2005 Golden Globe nomination for Best Actor in a Dramatic Series. He is currently single, devoting his time and energy to his leading role in Prison Break.

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