Jenny Slate

She and Gabe Liedman formed the comedy duo Gabe & Jenny. Their stand-up shows with Max Silvestri, "Big Terrific", were named best new variety show of 2008 by Time Out New York. In 2015, Slate, Liedman, and Silvestri ended the show, citing their busy schedules, though they have since occasionally performed together.

Slate first met Liedman in 2000 while attending Columbia University. They describe their relationship as a "nonsexual romance"; Slate says, "I like to think of us as kind of like [Seinfeld characters] Elaine Benes and George Costanza, but we like each other." Throughout 2008 and 2009, Slate regularly performed her one-woman show Jenny Slate: Dead Millionaire at the Upright Citizens Brigade Theatre (UCBT) in New York City.

Slate was a regular commentator on many VH1 "talking head" commentary programs. In early 2009, she had made several appearances on the Late Night with Jimmy Fallon recurring sketch "7th Floor West", where she played an NBC page also named Jenny, who was later promoted to Fallon's assistant. She had a recurring role in Bored to Death. Slate's guest appearances on television programs include Bob's Burgers, Girls, The Whitest Kids U' Know, Important Things with Demetri Martin and Raising Hope.

Slate joined the cast of Saturday Night Live for the 2009–10 season. In her first episode, she accidentally said "fucking" during her debut sketch "Biker Chick Chat", which was heard on the live broadcast, but removed from reruns. In various sketches, she impersonated Hoda Kotb, Lady Gaga, Kristen Stewart, Ashley Olsen, and Olympia Snowe. She was best known for Tina-Tina Cheneuse, an infomercial pitchwoman who advertises personalized doorbells, car horns, and alarm clocks. Slate's contract was not renewed for another season. Despite rumors to the contrary, Slate has insisted that her SNL termination was not due to cursing but rather simply because "I didn't click."

In August 2010, she co-wrote and voiced the animated short film Marcel the Shell with Shoes On. This led to Marcel the Shell with Shoes on, Two. Slate also wrote a "Marcel"-themed children's book that was released on November 1, 2011. Her first major film role was as Zoe in Alvin and the Chipmunks: Chipwrecked; more films followed in 2012, including the voice of Ted's mother in The Lorax.

Her first appearance in Parks and Recreation was in the 2013 episode "Bailout", in which she portrayed Mona-Lisa Saperstein. Following her success on the NBC show, Slate released and starred in a 12-episode mini-series on YouTube called Catherine, celebrating late 1980s and early 1990s soap-opera aesthetics. On July 23, 2013, she appeared in Drunk History retelling the history of how Coca-Cola was made.

In 2014, Slate starred in the comedy-drama film Obvious Child, which follows the life of a young stand-up comic as she grapples with an unplanned pregnancy and eventual abortion. Slate went on to win the Critics Choice Award for Best Actress in a Comedy, Best Breakout Performance at the Newport Beach Film Festival, the Virtuosos Award at the Santa Barbara International Film Festival, and Best Comedic Actress at the Women Film Critics Circle Awards for her performance in the film.

Slate co-starred with Judy Greer and Nat Faxon in the first season of the FX series Married. She left the series as a series regular in season two, but still appeared in a few episodes. Sarah Burns took her place in the series.

Slate appeared as Liz B. in the recurring "PubLIZity" sketches in Kroll Show, as well as many other recurring and one-off characters, performing in some capacity in almost every episode until the series ended in 2015. In 2016, Slate voiced Dawn Bellwether in the Disney animated comedy-adventure film Zootopia and Gidget in the animated feature The Secret Life of Pets.

Slate and her father co-wrote a book titled About the House, about their time living in Slate's childhood home in Milton, Massachusetts, which was published in December 2016.

In 2017, Slate starred in the film Gifted as Bonnie Stevenson, the teacher of a 7-year-old mathematical genius.

In October 2019, Slate released a stand-up comedy special on Netflix, titled Stage Fright.

Slate published her book titled Little Weirds, about her struggles with and thoughts about life and relationships, in 2019.

From 2017 until 2019, Slate voiced the biracial character Missy Foreman-Greenwald on the animated Netflix series Big Mouth. Slate exited the role on June 24, 2020, writing on Instagram that "At the start of the show, I reasoned with myself that it was permissible for me to play Missy because her mom is Jewish and White — as am I. But Missy is also Black and Black characters on an animated show should be played by Black people."

In 2022, Slate appeared in the critically acclaimed science fiction film Everything Everywhere All at Once as Big Nose. Her character's original name was changed to Debbie the Dog Mom for the film's digital release due to its association with Jewish stereotypes. For her performance, she won, along with the rest of the cast, the Screen Actors Guild Award for Outstanding Performance by a Cast in a Motion Picture.