McDonough was born in Dorchester, Massachusetts, the son of Catherine (née Bushe) and Frank McDonough, motel owners who emigrated from Ireland, with his mother coming from County Tipperary and his father from County Galway. McDonough grew up in Barnstable, Massachusetts and was raised Roman Catholic. His childhood nickname was "Headster", which McDonough says originated in his brothers\' teasing him about the size of his head. He graduated from Barnstable High School, and attended Syracuse University, where he was initiated and became a member of the Sigma Chi Fraternity and graduated with a Bachelor of Fine Arts degree in 1988. He had obtained several college scholarships to play baseball, but he decided to go to Syracuse as he thought it had the best theater department.\n', '

In 1991, McDonough won the Best Actor Dramalogue for "Away Alone". McDonough has made many television and film appearances since then, including Band of Brothers, Boomtown, Star Trek: First Contact, Minority Report and The Hitcher. McDonough played Dave Williams on the fifth season of Desperate Housewives. He also starred in the lead role on 2004 medical drama Medical Investigation for its one full season.\n', '

McDonough was set to star in the ABC dramedy Scoundrels, but was fired for refusing to act in sex scenes, citing his family and Catholic faith as basis for his decision.\n', '

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