Laurue Holden made a name for herself by co-starring opposite Burt Reynolds in Physical Evidence (1989), Vanessa Redgrave in Young Catherine (1991), and William Shatner in the TV Movie TekWar: TekLab (1994). She also played Mabel Dunham in the TV Movie The Pathfinder (1996) (based on the novel of James Fenimore Cooper). Onstage, she starred in Time and the Conways, written by J. B. Priestley, and The Winter’s Tale, based on the play by William Shakespeare. Other stage roles include Regina in Ghosts and Procne in The Love of the Nightingale.
After making various guest appearances on Due South, Murder, She Wrote, and Poltergeist: The Legacy (when she played a dual role), Holden found success playing a recurring role on the seminal sci-fi series The X-Files: Marita Covarrubias, a mysterious government worker who becomes an informant to Special Agent Fox Mulder, from seasons four through nine (1996–2002).
She also had a supporting role, as Mary Travis, opposite Michael Biehn and Ron Perlman, in the CBS TV series based on the MGM classic, The Magnificent Seven (1998–2000) and a role as Debra Campbell on Highlander: The Series.
Some of Holden’s most notable roles include starring opposite Jim Carrey in Frank Darabont’s film The Majestic (2001) (It was while performing on stage in Cat on a Hot Tin Roof, that Holden was discovered by Darabont). As Carrey’s long lost love, she received critical acclaim for her performance. She also co-starred alongside Dean Cain, Jennifer Tilly, and Tim Curryin the Canadian comedy Bailey’s Billion$. Other movie roles have included those of Michael Chiklis’ character’s former love interest in Fantastic Four (2005), Cybil Bennett in Christophe Gans’ artistic-horror video game adaptation of Silent Hill (2006), Amanda Dumfries in The Mist (2007).
In 2008, she joined the final season of TV Series The Shield, where she played Olivia Murray.
From 2010 to 2013, she played the role of Andrea, a civil rights attorney and survivor of a global zombie plague in The Walking Dead.
In 2013, she worked on the movie Honeytrap as an executive producer. In 2014 she played the role of Ann McGinnis in the third season of Major Crimes. Also in 2014, she co-starred in the movie Dumb and Dumber To, opposite Jim Carrey, Jeff Daniels and Kathleen Turner. She played Adele Pinchelow, the main antagonist of the Farrelly brothers comedy.
In 2015, she appeared as Dr. Hannah Tramble, an ER surgeon, in the third season of Chicago Fire.
In 2016, she appeared in The Abolitionists, a documentary film by Darrin Fletcher. In 2017, Holden joins the cast of The Americans in the fifth season, when she plays Renee. She was cast in indie thriller Pyewacket, a movie directed by Adam MacDonald.
In 2018, Laurie Holden appeared in the crime thriller Dragged Across Concrete, starring Mel Gibson and Vince Vaughn.
Holden joined the cast of American legal drama television series Proven Innocent (which premiered in 2019 on Fox), where she plays Greta Bellows.
In 2022, she joins The Boys season 3, in the role of Crimson Countess, while also performing the songs “America’s Son” and “Chimps Don’t Cry”.