She is best known for playing Karen Walker in the NBC sitcom Will & Grace (1998–2006, 2017–2020), for which she received eight Primetime Emmy Award nominations for Outstanding Supporting Actress in a Comedy Series, winning twice, in 2000 and 2006.
She has also appeared in guest spots and recurring roles on other comedy series including, Happy Endings, Bob's Burgers, Parks and Recreation, 30 Rock, Up All Night, Boston Legal, The New Adventures of Old Christine, and The Great North.
Following her graduation from Casady School in Oklahoma City,[6] Mullally attended Northwestern University in Evanston, Illinois, where she studied English literature and art history.
She subsequently guest-starred on sitcoms such as Seinfeld, Frasier, Wings, Herman's Head, Ned and Stacey, Mad About You, Caroline in the City, 3rd Rock from the Sun and Just Shoot Me!.
Mullally guest-starred as an adoption case worker for Liz Lemon in the third-season premiere of the NBC sitcom 30 Rock and returned to play the same character two additional times during the show's run.
In 2011, Mullally began a recurring role as Dana Hartz, the mother of Penny (Casey Wilson), on the ABC sitcom Happy Endings.
On 3 April 2014, she portrayed Miss Adelaide in a one night only concert of Guys and Dolls opposite Nathan Lane, Sierra Boggess and Patrick Wilson at Carnegie Hall From April 13 to June 1, 2014, Mullally starred alongside her real-life husband, Nick Offerman, in Annapurna at the off-Broadway Acorn Theatre on New York's 42nd Street Theatre Row.
[15] In 2014 Mullally starred in the Broadway performance of It's Only a Play with F. Murray Abraham, Matthew Broderick, Stockard Channing, Rupert Grint, Nathan Lane and Micah Stock.
[16] In June 2021, Mullally was set to appear as "Reno Sweeney" in Anything Goes at the Barbican Theatre in London for a strictly limited season, but had to pull out due to an injury.
Nancy & Beth performed at Lincoln Center as part of its American Songbook Series on February 13, 2019, and toured the US in April and May 2019, beginning in Los Angeles and ending in New York City.
[22][23] Mullally has appeared in Marc Forster's Sundance competition entry Everything Put Together, Anywhere but Here with Susan Sarandon and Natalie Portman, About Last Night with Demi Moore and Rob Lowe, Speaking of Sex with James Spader, and Stealing Harvard with Tom Green and Jason Lee.
Additionally, Mullally sang the song "Long John Blues" (performed on-screen by Kristen Bell) in 2010's Burlesque.
In 2017, Mullally appeared in Janicza Bravo's first full-length feature, Lemon, which debuted at Sundance Film Festival.
[26] On October 6, 2023, A24's Dicks: The Musical was released, starring Mullally[27] alongside Nathan Lane, Megan Thee Stallion, and the movie's writers, Josh Sharp and Aaron Jackson.
Mullally and husband Nick Offerman wrote The Greatest Love Story Ever Told, published by Dutton on October 2, 2018.
[28] Mullally's first marriage was to James Thomas Hines in 1982 at Los Angeles, they separated without having children, and their divorce finalized in 1987 at the same city.
[29] A few years later in 1992 she married Michael Katcher, a talent agent, at Los Angeles, they separated without dissent, and their divorce was finalized in 1996.
[30][31] Mullally met actor and future husband Nick Offerman in 2000 while acting in The Berlin Circle,[32] a play produced by the Evidence Room Theatre Company, and she married for a third time, three years later in 2003.
The couple have also appeared together in films such as The Kings of Summer and Smashed and the television series Parks and Recreation and The Umbrella Academy, and they also performed voice work together in Bob's Burgers, Hotel Transylvania 2, and The Great North.