He has over thirty screen credits to his name, most of them in villainous or antagonistic roles such as Never Say Never Again, Superman III, Death Wish 3 and The Last Outlaw. His role as Airk Thaughbaer in the 1988 fantasy Willow is one of the few heroic roles that he has portrayed, as well as that of the dashing British officer from Virginia Captain Leroy in Sharpe's Eagle.
He appeared in Rich Man, Poor Man and Tales From The Crypt. In 1994, he starred as John Garrideb in "The Mazarin Stone" from Granada TV's Sherlock Holmes series. The events of the story were rewritten and merged with The Adventure of the Three Garridebs.
He was cast as the eldest sibling, Chuck Cunningham, on Happy Days. He was eventually replaced by Randolph Roberts until the episode "Guess Who's Coming to Christmas". Chuck was not seen again but was later mentioned in a few other episodes ending with "Fish and the Fins". After that, Chuck was written off the show completely with later episodes depicting the Cunningham family with only two children with Richie as the eldest. The character gave rise to the pejorative term "Chuck Cunningham Syndrome", referring to characters who disappear from TV shows without explanation and are later retconned to have never existed. O'Herlihy did not want to become stuck in television roles, preferring films. He played a warrior in the George Lucas production Willow, directed by his Happy Days brother, Ron Howard. He also appeared in the pilot episode of Star Trek: Voyager, "Caretaker", as the Kazon First Mate, Jabin. He also appeared in The Six Million Dollar Man and The Bionic Woman television series.
O'Herlihy was cast as sadistic killer Dan Suggs in the 1989 miniseries Lonesome Dove.
By the 1990s O'Herlihy had permanently relocated to the UK where he has preferred to work in the theatre and on television, with roles on British television, including Coded Hostile, Sharpe, Jonathan Creek, and Midsomer Murders.
In 2009 O'Herlihy returned to the big screen as Sheriff Vaines in the follow up to Neil Marshall's cult horror film, The Descent 2, and over a decade later returned to the screen again to play the leading role of writer John Anderson for director Nic Saunders in Queen of the Redwood Mountains, a film inspired by the authors of the Beat Generation, and due for release in 2021.
- Happy Days (1974) - Charles "Chuck" Cunningham
- The California Kid (1974) - Tom
- A Death in Canaan (1978) - Father Mark
- A Wedding (1978) - Wilson Briggs
- A Rumor of War (1980) - Stanton
- We'll Meet Again (1982) - Captain "Red" Berwash
- Superman III (1983) - Brad Wilson
- Never Say Never Again (1983) - Captain Jack Petachi
- The Secret Adversary (1983, TV Movie) - Julius P. Hersheimmer
- The Dirty Dozen: Next Mission (1985, TV Movie) - Conrad E. Perkins
- Death Wish 3 (1985) - Manny Fraker
- A Killing on the Exchange (1987)
- Willow (1988) - Airk Thaughbaer
- Space Riders (1989) - Ron Harris
- Lonesome Dove (1989) - Dan Suggs
- Twin Peaks (1990) - Preston King
- Conagher (1991) - Chris Mahler
- The Last Outlaw (1993) - Marshal Sharp
- Sharpe's Eagle (1993) - Captain Leroy
- "The Mazarin Stone" (1994) - John Garrideb
- The Shooter (1995) - Dick Powell
- Prince Valiant (1997) - King Thane
- Top of the World (1997) - Lieutenant Logan
- Command Approved (2000) - Arms Dealer
- Butterfly Man (2002) - Bill Kincaid
- Seven Days of Grace (2006) - MacNab
- The Descent Part 2 (2009) - Vaines
- Queen of the Redwood Mountains (2021) - John Anderson
- Lynch, Donal (2013-09-16). "happy daYS in dublin: Gavan O'Herlihy talks about 'Waiting For Godot' and why he passed up the chance of being a millionaire by 24". Irish Independent. Retrieved 2017-11-04.
- Brant, Marley (2006). Happier Days: Paramount Television's Classic Sitcoms, 1974-1984. Billboard Books. p. 32. ISBN 9780823089338.
- What happened to Richie's brother "Chuck" from "Happy Days?"
- Abramson, Dan (June 17, 2010). "The 13 Most Ridiculous Sitcom Mysteries Of All Time (PHOTOS)". huffingtonpost.com.