In 1986, Charles headlined a production of Jonathan Marc Sherman's Confrontation. In 2004, he appeared on stage in New York in a revival of Neil LaBute's The Distance From Here, which received a Drama Desk Award for Best Ensemble Cast. In January 2006 he appeared in the world premiere of Richard Greenberg's The Well-Appointed Room for the Steppenwolf Theatre Company in Chicago, and followed this with a run at the American Conservatory Theater in San Francisco, portraying the cloned brothers in Caryl Churchill's A Number. In 2007, he appeared in Adam Bock's The Receptionist at the Manhattan Theatre Club. In 2011, Charles was the narrator for NFL Network's A Football Life's debut episode on New England Patriots head coach Bill Belichick.
Charles's film debut was in fellow Baltimore native John Waters' Hairspray in 1988. The following year, he starred alongside Robin Williams and Ethan Hawke in the Oscar-winning Dead Poets Society. Subsequent film roles have included Don't Tell Mom the Babysitter's Dead, Threesome, Pie in the Sky, Muppets from Space, S.W.A.T, Four Brothers, After.Life, Crossing the Bridge, and Brief Interviews with Hideous Men.
On television, Charles played Sports anchor Dan Rydell in Aaron Sorkin's Emmy Award-winning Sports Night, which ran for two years (1998–2000) on ABC and earned Charles a Screen Actors Guild nomination. In 2008, Charles played the role of Jake in Season 1 of HBO's In Treatment. In 2009, he returned to network television in the CBS drama The Good Wife. For his work on the series he was nominated for a Primetime Emmy Award for Outstanding Supporting Actor in a Drama Series in 2011 and 2014.
In September 2013, Charles married ballet Dancer and author Sophie Flack. On December 9, 2014, Flack gave birth to the couple's first child.
