Her best known movie role is as the Vestal Virgin Miriam in Mel Brooks's History of the World, Part I. Her best known television role was as Gail Leery on "Dawson's Creek". Humes has also appeared on such television series as Grey's Anatomy, The Dukes of Hazzard, Matlock, Knight Rider, Murphy Brown, The A-Team, The Fall Guy, Hardcastle and McCormick, T.J. Hooker, Riptide, and Touched by an Angel. She was also a regular on the short-lived NBC series Eerie, Indiana in 1990. In 2000, she portrayed Hazel Show in The Stalking of Laurie Show, a made-for-television movie.