Alongside Gabe Liedman, Slate was half of the comedy duo Gabe & Jenny.
Their live stand-up shows with Max Silvestri titled Big Terrific were named best new variety show of 2008 by Time Out New York.
In 2015, Slate, Liedman, and Silvestri announced that the show would be ending due to their busy schedules, though they continue to perform together when possible.

Slate first met Liedman in 2000 while attending Columbia University.
They describe their relationship as a "nonsexual romance" and Slate says, "I like to think of us as kind of like Elaine Benes and George Costanza, but we like each other."
 Throughout 2008 and 2009, Slate regularly performed her one-woman show titled 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 also had a recurring role in Bored to Death.
Slate has made guest appearances on television programs, such as 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 one season from 2009 to 2010.
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.
During her brief time on the series, she impersonated celebrities such as Hoda Kotb, Lady Gaga, Kristen Stewart, Ashley Olsen, and Olympia Snowe and became 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 film Marcel the Shell with Shoes On, which garnered viral success.
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 Film Festival, and Best Comedic Actress at the Women Film 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
Alongside Gabe Liedman, Slate was half of the comedy duo Gabe & Jenny. Their live stand-up shows with Max Silvestri titled Big Terrific were named best new variety show of 2008 by Time Out New York. In 2015, Slate, Liedman, and Silvestri announced that the show would be ending due to their busy schedules, though they continue to perform together when possible.
Slate first met Liedman in 2000 while attending Columbia University. They describe their relationship as a "nonsexual romance" and Slate says, "I like to think of us as kind of like Elaine Benes and George Costanza, but we like each other."  Throughout 2008 and 2009, Slate regularly performed her one-woman show titled 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 also had a recurring role in Bored to Death. Slate has made guest appearances on television programs, such as 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 one season from 2009 to 2010. 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. During her brief time on the series, she impersonated celebrities such as Hoda Kotb, Lady Gaga, Kristen Stewart, Ashley Olsen, and Olympia Snowe and became 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 film Marcel the Shell with Shoes On, which garnered viral success. 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 Film Festival, and Best Comedic Actress at the Women Film 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
Jenny Slate