Miller's father "is African-American, Jamaican, English, German" and part Cherokee and Jewish; his mother is Russian, French, Dutch, Syrian, and Lebanese. In an interview, Miller said: "My father is black and my mother is white. Therefore, I could answer to either which kind of makes me a racial Lone Ranger, at times, caught between two communities."

He was born in Chipping Norton, Oxfordshire, England, where his father, a Rhodes Scholar, was living while studying at Oxford. His family moved to Park Slope, Brooklyn, New York, when he was one. He has two sisters, Leigh and Gillian. Miller attended Midwood High School in Brooklyn, New York, USA. He was a member of SING!, an annual musical production that was started by Midwood. He graduated from Princeton University with a degree in English Literature. While at Princeton, he performed with the school's a cappella group, The Princeton Tiger Tones. In 1995, he went to Los Angeles to pursue an acting career.

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, he moved on to co-star in the 2003 film The Human Stain, playing the younger version of Anthony Hopkins' character. Miller's first TV appearance was as student-turned-sea monster Gage Petronzi on Buffy the Vampire Slayer ("Go Fish," 1998).

Miller further enhanced his profile in 2005 by obtaining the starring role as Michael Scofield in Fox Network's television drama Prison Break, in which he played the role of a caring brother who created an elaborate scheme to help his brother, Lincoln Burrows (Dominic Purcell) escape death row after being found guilty of a crime he didn't commit. His performance in the show earned him a 2005 Golden Globe nomination for Best Actor in a Dramatic Series.

Miller recently says that he credits Mariah Carey with giving him his big break when she asked him to appear in the video for her single, We Belong Together.

He tells the Daily Star: “Mariah’s an international icon. The two days I spent working on her video did more for my career, gave me more exposure, than anything I’d done before Prison Break.

• Wentworth Miller at the IMDB
• Wentworth Miller at TV.com
• Wentworth Miller's biography at Prison Break's official website
• Broadband video interview with Wentworth Miller, discussing Prison Break
• Interview with Wentworth on WHO.com
• Wentworth Miller Bio