McCrane was born in Philadelphia, Pennsylvania, the son of Eileen C. (née Manyak), a nurse, and James J. McCrane, Jr., an actor and Writer. He has a brother, Jim, and three sisters, Maureen, Barbara, and Deirdre. His family moved to Richboro, Pennsylvania, where he lived until he moved to New York City after graduating from Holy Ghost Preparatory School in 1978.
Later, he played murderous Emil Antonowsky in RoboCop, followed by Astronaut Pete Conrad in From the Earth to the Moon, Guard Trout in The Shawshank Redemption, cancer-absorbing mutant Leonard Betts in The X-Files. After a recurring role as the snarky Dr. Robert "Rocket" Romano on ER, he became a regular cast member (1997–2003) and returned for one episode during its 15th and final season (2008). McCrane guest-starred in 24 Seasons 5 and 6 as Graem Bauer. He has also appeared on Ugly Betty and CSI: Crime Scene Investigation.
McCrane married Dana Kellin, a jewelry designer, in 1998. They have two children, william Thomas and Noa Cathryn. McCrane and Kellin met in a yoga class in 1996.
In 2011, McCrane took on the recurring role of Assistant District Attorney Josh Peyton in the NBC television program Harry's Law, a project of Producer David E. Kelley. McCrane won the 2011 Emmy Award for Guest Actor in a Drama Series for his performance in the role.
