James R. Guthrie appeared in the Los Angeles production of Baz Luhrmann's La Bohème as the Mad Old Drag Queen (Ovation Award, best ensemble).

He has appeared with Lincoln Opera, Metro Lyric Opera, Regina Opera, Denver Opera Company, New York Chamber Opera, Opera Colorado, Lyric Opera of Chicago and San Francisco Opera. He performed Ubaldo Piangi in the national tour of The Phantom of the Opera and can be seen as Canio in Pagliacci in Brian De Palma's 1987 film The Untouchables.