Television
In the late 1980s, she was hired to perform with Second City's touring company. It was there she met Paul Dinello and Stephen Colbert, with whom she often collaborated later in her career. She and Dinello did not get along with Colbert at first, but they became close friends while touring together, discovering that they shared a similar comic sensibility. Sedaris left Second City in 1993, and moved to New York City. Sedaris's first major foray into television began in 1995 on the Comedy Central sketch series Exit 57, alongside Colbert and Dinello. For her performance she was nominated for the 17th CableACE Award for Best Comedy Actress and the series was nominated for Best Comedy Series. It ran for a total of two seasons.
Beginning in 1999 Sedaris played Jerri Blank, a middle-aged woman who goes back to high school in the Comedy Central comedy series Strangers with Candy. The series, which she co-wrote with Dinello and Colbert, was based on Sedaris's impression of 1970s-era motivational speaker Florrie Fisher. The show ran for three seasons. In 2005, a film adaptation was released, acting as a prequel to the series.
Sedaris went on to make numerous guest appearances on television programs, including Just Shoot Me! (2001), Sex and the City (2002–2003), Monk (2002–2003), Wonder Showzen (2005), My Name Is Earl (2006), Sesame Street (2006), Rescue Me (2007), The Closer (2009), The New Adventures of Old Christine (2009), The Middle (2010), Raising Hope (2011–2014), and The Good Wife (2012). She also hosted the series Film Fanatic on Trio.
Sedaris's talk show appearances include Late Show with David Letterman, The Late Show with Stephen Colbert, Late Night with Conan O'Brien, Jimmy Kimmel Live!, The Late Late Show with Craig Ferguson, The Daily Show, The Colbert Report, Late Night with Jimmy Fallon, and WTF with Marc Maron. During an appearance on Chelsea Lately, she gave host Chelsea Handler a presentation on vaginal hygiene using a plush vagina created by fashion designer Todd Oldham.
In 2008, Sedaris starred as Principal Abby Hofman in the Nickelodeon television film Gym Teacher: The Movie, which was directed by her Strangers with Candy co-star and frequent collaborator Paul Dinello.
In early 2010, she had a supporting character in the Canadian comedy series The Drunk and On Drugs Happy Fun Time Hour. Later in 2010 she appeared alongside Paul Dinello in the episode "Mummified Hand", of the Discovery/Science Channel documentary series Oddities.
In 2011, she appeared in a series of commercials for Downy (Lenor UK) Unstoppables, a fabric softener product. Grey Global Group designed the commercials as "kicking the old 'mom' image with spots featuring 'laundry expert' (and accomplished lifestyle guru) Amy Sedaris".
In 2013, she replaced Kristen Schaal as the sex-crazed Hurshe Heartshe, in the second season of the Adult Swim comedy series The Heart, She Holler. She also appeared in the third and final season. That same year, Sedaris appeared in a major recurring role in the Amazon Prime Video political satire series Alpha House, which was written by Doonesbury creator Garry Trudeau. Sedaris played Louise Laffer, the Mormon wife of Nevada Senator Louis Laffer who lives with three other Republican senators in a town house on Capitol Hill.
Sedaris later had a recurring role as Pam in the Comedy Central sitcom Broad City (2014–2019), as Rita in the Hulu dark comedy series Difficult People (2015–2017). From 2015 to 2020, she portrayed Mimi Kanasis in the Netflix comedy series Unbreakable Kimmy Schmidt, for which she earned a nomination for the Gold Derby Award for Best Comedy Guest Actress.
In 2016, Sedaris appeared in the tragicomedy series Horace and Pete, as a character named Mara looking for a job at Horace and Pete's. She also co-starred with Chris Elliott in the Sony Crackle family comedy series Thanksgiving.
In 2017, Sedaris created the TruTV surreal comedy series At Home with Amy Sedaris, which she also wrote and executive produced. The series focused on the comedian's love of entertaining, crafts, and cooking. She played numerous characters, including herself, Patty Hogg, Ronnie Vino, and Nutmeg. The series was met with critical acclaim upon its premiere, garnering two consecutive nominations for the Primetime Emmy Award for Outstanding Variety Sketch Series, and ran for three seasons.
Sedaris had a starring role as Janice Delongpre, a dispatch officer, in the CBS All Access comedy series No Activity from 2017 to 2019. She had guest-starring roles as Cathy in the HBO comedy-drama series Divorce (2018).