Known for playing starring and recurring roles in comedic television, her accolades include one Golden Globe, five Primetime Emmys and two Screen Actors Guild Awards.

Lynch gained recognition for her collaborations with Christopher Guest, appearing in the mockumentary films Best in Show (2000), A Mighty Wind (2003), and For Your Consideration (2006).

Lynch is also known for her stage work including her role in Nora Ephron's off-Broadway play Love, Loss, and What I Wore in 2009.

Lynch spent 15 years in Chicago, acting in the Steppenwolf Theatre Company and, at the time of her audition, was one of only two women picked to join The Second City comedy troupe.

During the 1990s, she made numerous television commercials, including one for Frosted Flakes for an adult audience, directed by Christopher Guest.

Lynch played Christy Cummings, a butch lesbian personal dog handler to trophy wife Sheri Ann Cabot (Jennifer Coolidge).

From there, she became a staple actress in Guest's casts, appearing in the director's A Mighty Wind (2003) as porn actress-turned-folk singer Laurie Bohner and in For Your Consideration (2006) as an entertainment reporter.

She told Fresh Air's Terry Gross that the role was originally intended for a man but also that, at the urging of Steve Carell's wife Nancy Walls, it was offered to Lynch instead.

[18] From there, she took supporting roles in a series of films including Role Models, Talladega Nights: The Ballad of Ricky Bobby, Alvin and the Chipmunks, Walk Hard: The Dewey Cox Story, Space Chimps, The Rocker, The Hammer, Another Cinderella Story, Ice Age: Dawn of the Dinosaurs, Wreck-It Ralph and Spring Breakdown.

Entertainment Weekly dedicated an article on its website to the possibility of her performance receiving an Academy Award nomination.

Lynch has appeared in many television series, including The X-Files, L.A. Law, Judging Amy, The West Wing, 7th Heaven, Glee, Desperate Housewives, Friends, NewsRadio, Married With Children, 3rd Rock From The Sun, Dawson's Creek, Felicity, Arrested Development, Lovespring International, Two and a Half Men, Veronica Mars, Weeds, Boston Legal, L Word, Criminal Minds, Help Me Help You, Gilmore Girls, New Adventures of Old Christine, Psych, Monk, The Marvelous Mrs. Maisel, The King of Queens and Frasier.

She also starred with John Hannah and William Fichtner in 2002's MDs and has appeared in the crime drama Criminal Minds as Spencer Reid's schizophrenic mother.

The role echoed previous guest appearances in The X-Files and Veronica Mars, being her third time cast as a harsh high school teacher.

Mary McNamara of the Los Angeles Times wrote, "Lynch alone makes Glee worth watching.

[31] Also in 2017, Lynch guest-starred in Episode 7 of Marvelous Mrs Maisel as popular but dislikeable comic Sophie Lennon.

Lynch has played recurring character Sazz in the Hulu/Disney+ comedy mystery series Only Murders in the Building since its beginning in 2021.

Lynch was inspired to write the book after reflecting upon the successes of her past year and wishing she could have told her more anxious, younger self to not worry as much.

In March 2012, Lynch was featured with Martin Sheen, Jamie Lee Curtis, Chris Colfer and Brad Pitt in a performance of Dustin Lance Black's play 8 – a staged re-enactment of the federal trial that overturned California's Prop 8 ban on same-sex marriage – as Maggie Gallagher.

[51] The production was held at the Wilshire Ebell Theatre and broadcast on YouTube to raise money for the American Foundation for Equal Rights.

[52][53] Lynch made her Broadway debut as Miss Hannigan in Annie for a limited engagement lasting from May 15 to July 14, 2013.

[58] In 2022, Lynch was named honorary "mayor of Funner", the putative location of Harrah's Resort Southern California.