Theodore Raymond Knight was born on March 26, 1974, in Minneapolis, Minnesota. At 5 years old, he became involved with the Guthrie Theater. He attended Annunciation Catholic School from kindergarten to eighth grade. He received the Conners Foundation Scholarship as a freshman and apprenticed at the Children's Theatre Company. He worked at the local Red Owl supermarket with his brother. After graduating the Academy of Holy Angels in Richfield, he enrolled at the University of Minnesota. He dropped out and soon landed roles at the Guthrie Theater.
He moved to New York City and appeared on the broadway. In 2001, he starred in the revival of Noises Off. In 2003, he performed Tartuffe and Scattergood. In 2004, he starred in a off-broadway production, Boy.
In 2003, he made his television debut on the CBS television series, Charlie Lawrence.
In 2005, he was cast as George O'Malley on the ABC medical drama Grey's Anatomy. He played as a surgical intern at the fictional Seattle Grace Hospital. He worked his way up to resident level, while his relationships with his colleagues Meredith Grey (Ellen Pompeo), Cristina Yang (Sandra Oh), Izzie Stevens (Katherine Heigl) and Alex Karev (Justin Chambers) formed a focal point of the series. When he auditioned for the show, he expected the show to be on for one season. In 2009, it was confirmed that he would not be returning for the shows sixth season. He stated that the reason for his departure was due to his character's lack screen time, as well as coming out as gay.
In 2009, he starred in the production of the musical Parade. In 2010, he returned to Broadway in A Life in the Theatre.