- Decided to give up on acting until his manager got him a meeting and audition for Band of Brothers (2001). His work on that led to Steven Spielberg casting him in Minority Report (2002).
- In grade school, his first acting role was that of the Cowardly Lion in "The Wizard of Oz". According to McDonough, he really wanted to play the Tin Man. In 2007, he finally got his chance, appearing in the title role of Sci-Fi Network (now Syfy)'s miniseries Tin Man (2007).
- According to Nathan Fillion in his appearance on the Nerdist podcast, Neal McDonough was also under consideration for the part of Captain Malcolm Reynolds on Firefly (2002).
- He has dual US and Irish citizenship.
- Played the voice of Oliver Queen/Green Arrow in the 2010 animated short film "Green Arrow" and played Damien Darhk (enemy of Green Arrow) in the live-action TV series "Arrow" (2012).
- In a 2019 speech, he said that when accepting roles in multiple productions he stipulated that he would not kiss or do sex scenes with anyone other than his wife. This led to him being blackballed for many years, causing his family significant hardship.
- He has played the same character (Damien Darhk) in three different series: Arrow (2012), The Flash (2014) and DC's Legends of Tomorrow (2016).
- His parents are Catherine and Frank McDonough, both of whom emigrated from Ireland, with his mother coming from County Tipperary, Province of Munster, and his father from County Galway, Province of Connacht.
- Received his Bachelor's degree in Fine Arts from Syracuse University in 1988.
- His brother Gerard appeared as a contestant on an episode of "Who Wants to Be a Millionaire". He left with $32,000 after giving the incorrect answer for the $64,000 question.
- Is one of 6 children, has 4 brothers and one sister.
- Was named Mr. BHS in his senior year at Barnstable High School (a male spoof on the Junior Miss Pageant).
- Is a huge fan of Warren Zevon.
- His brother John is a former writer for national newspapers and currently teaches writing at the University of Massachusetts - Dartmouth.
- Daughter, Catherine "Cate" Maggie McDonough (born May 14, 2007), with Ruvé McDonough.
- Son, Morgan McDonough (born November 28, 2005), with Ruvé McDonough.
- His character Lieutenant Hawk in Star Trek: First Contact (1996) was originally written as the first openly gay character in any Star Trek series or movie, but all references to his sexual orientation were written out of later drafts of the screenplay. The character was later confirmed as having been gay in the Star Trek tie-in novel "Section 31: Rogue" by Andy Mangels and Michael A. Martin.
- Very good friends with Adrien Brody.
- Attended and graduated from Barnstable High School in Barnstable, Massachusetts.
- Is a member of Sigma Chi Fraternity.
- Like his Tin Man (2007) co-star Zooey Deschanel, he appeared in advertising for the clothing chain The Gap Inc.
- He guest starred in two unrelated television series featuring a regular character named Sam Beckett: China Beach (1988) and Quantum Leap (1989).
- Daughter, London Jane McDonough (b. January 11, 2010), with Ruvé McDonough. London weighed 7.95 lbs and measured 19 inches long.
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