Wyle was the only major cast member of ER to have been with the show since its inception when he left after its eleventh season. His performances on the show earned him Emmy Award nominations in each of its first five seasons, and (as part of an ensemble) several Screen Actors Guild Awards and nominations. Wyle left the series at the end of the 2004-2005 season, although he returned in guest appearances for four episodes in each of the next two seasons. He stated that he left because he wanted to spend more time with his family.

Wyle was born in Hollywood, California, to parents Stephen Wyle and Marjorie Speer, and was one of six children in a Reform Jewish home. He attended The Thacher School and graduated with the class of 1989. He married make-up artist Tracy Warbin on May 6, 2000. Together they have son Owen Strausser Wyle, born November 9, 2002 and daughter Auden Wyle, born October 15, 2005. He and his family are vegetarians.

Participated in a theater arts program at Northwestern University during high school and appeared in high school plays. After graduation he studied with acting teacher Larry Moss while living in a small apartment on Hollywood Boulevard. His first parts were a mini-series and featuring in the movie Crooked Hearts (1991) in 1990. In 1990 he worked in another feature, "There Goes My Baby." After appearing in several local plays in Los Angeles, he was cast in the box-office hit "A Few Good Men," in which he played a Marine jeep driver who testified in court. He also appeared in the feature "Swing Kids" as a leader in the Hitler Youth, and in The Myth of Fingerprints with Roy Scheier and Blythe Danner. Additionally, he starred as Lancelot opposite Sheryl Lee in the TV movie Guinevere.

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