Slate wrote the script for a reboot of the Looney Tunes franchise for Warner Bros. She co-created and voiced Marcel, a talking shell with an Oobi eye and a pair of doll shoes, in Marcel the Shell with Shoes On.
Slate's first major role in a film was as Zoe, an antagonist, from Alvin and the Chipmunks: Chipwrecked. She starred in Obvious Child, which won her the Critics' Choice Movie Award for Best Actress in a Comedy.
She also provided the voices of Mrs. Wiggins, Ted's mom, in The Lorax, Gidget in The Secret Life of Pets and The Secret Life of Pets 2, Harley Quinn in The Lego Batman Movie, and Valerie Da Vinci in Despicable Me 3. She also voiced Miss Nanny in the reboot series Muppet Babies.
- Jenny Slate was a guest star on the HBO show Hello Ladies which starred Nate Torrence.
- She appeared in the 2017 film Gifted with Octavia Spencer.
- She starred in House of Lies with Kristen Bell.
- She co-starred with Alan Tudyk in Alvin and the Chipmunks: Chipwrecked.
- She co-starred with Jason Bateman in The Longest Week.