Asner voice acting career includes playing George F. Babbitt, in the L.A. Classic Theatre Works' 1987 radio theatre production of Sinclair Lewis's novel, Babbitt. He also provided the voices for Joshua on Joshua and the Battle of Jericho (1986) for Hanna-Barbera, J. Jonah Jameson on the 1990s animated television series Spider-Man (1994-98); Hoggish Greedly on Captain Planet and the Planeteers (1990-95); Hudson on Gargoyles (1994-96); Jabba the Hutt on the radio version of Star Wars; Master Vrook from Star Wars: Knights of the Old Republic and its sequel; Roland Daggett on Batman: The Animated Series (1992-94); Cosgrove on Freakazoid!; Ed Wuncler on The Boondocks (2005-14); and Granny Goodness in various DC Comics animated series.

Asner also provided the voice of famed American orator Edward Everett in the 2017 documentary film The Gettysburg Address.
Asner is best known to many as the voice of Carl Fredricksen in the Academy Award-winning Pixar film Up (2009). He received great critical praise for the role, with one critic going so far as to suggest "They should create a new category for this year's Academy Award for Best Vocal Acting in an Animated Film and name Asner as the first recipient."