Meaney was born in Dublin. He started studying acting when he was fourteen years of age, and entered the Abbey Theatre School of Acting after secondary school. He became a member of the Irish National Theatre and spent the next eight years in England, touring with several theatre companies.

Meaney's first television appearance was in Z-Cars on BBC1 in 1978. He guest-starred on shows such as Remington Steele and Moonlighting before embarking on a successful film career; he received a Golden Globe nomination for Best Actor for his role in The Snapper.

Meaney first appeared on Star Trek: The Next Generation in 1987 in its pilot episode, Encounter At Farpoint. His character was eventually given the name of Miles O'Brien. In 1993, Meaney left The Next Generation for its spin-off Star Trek: Deep Space Nine, and remained on Deep Space Nine until its final episode in 1999. With 225 total appearances on Star Trek (173 on Deep Space Nine and 52 on The Next Generation), he has made more appearances on the franchise than any other actor except Michael Dorn (280). Meaney appeared in two Star Trek pilot episodes (The Next Generation and Deep Space Nine), a distinction shared with Patrick Stewart and Armin Shimerman. Meaney is also one of six actors to appear in the finales of two different Star Trek series.

He has also played a minor recurring role as Cowen, leader of the Genii on the Sci-Fi Channel series Stargate Atlantis, guest-starred on Law & Order: Criminal Intent and appeared as Bob O'Donnell on the ABC show Men In Trees.

He was the only actor to appear in all three film adaptations of Roddy Doyle's The Barrytown Trilogy wherein he played the father of the Rabbitte family; however due to rights issues the family name changed from film to film.

His stage appearances include the Old Vic production of Eugene O'Neill's A Moon for the Misbegotten.

Colm starred in British comedy film Three and Out released in the UK on 25 April, 2008.

Meaney was married to Irish actress Bairbre Dowling, but they are now divorced. He remarried in March 2007 to Ines Glorian. He is a fan of Dublin's gaelic football team and Shamrock Rovers.

He is unrelated to the science fiction writer John Meaney, though the latter does have a brother who is also named Colm.

• The Dead (1987).....Mr. Bergin
• Die Hard 2 (1990).....Pilot
• Dick Tracy (1990).....Cop at Tess's
• The Commitments (1991).....Jimmy Rabbitte, Sr.
• Under Siege (1992).....Doumer
• The Last of the Mohicans (1992).....Maj. Ambrose
• Far and Away (1992).....Kelly
• Into the West (1992).....Barreller
• The Snapper (1993).....Dessie Curley
• War of the Buttons (1994).....Geronimos' Dad
• The Road to Wellville (1994)....Dr. Lionel Badger
• The Englishman Who Went Up a Hill But Came Down a Mountain (1995)....Morgan the Goat
• The Van (1996).....Larry
• Con Air (1997).....DEA Agent Duncan Malloy
• Owd Bob (1997)
• This Is My Father (1998)....Seamus, Owner of the Bed-and-Breakfast
• Monument Ave. (1998)
• Mystery, Alaska (1999)
• The Magical Legend of the Leprechauns (1999)....Seamus Muldoon
• How Harry Became a Tree (2001).....Harry
• The Boys From County Clare (2003).....Jimmy
• Intermission (2003).....Jerry Lynch
• Layer Cake (2004).....Gene
• Five Fingers (2006) .... Gavin
• The Unit (2006).....Charge D'Affaires
• Caved In: Prehistoric Terror (2006).....Vincent
• A Lobster Tale (2006) .... Cody
• Kings (2007)
• Clean Break (2008) .... Trevor Jones
• Three and Out (2008) .... Tommy
• The Damned United (2009) .... Don Revie