Shearer was later a member of Los Angeles radio comedy group The Credibility Gap, 1968-1974, and regular on Saturday Night Live in 1979-1980 and 1984-1985, leaving for good midseason in January 1985 over "creative differences." When reached for comment over the nature of his departure, Shearer replied "I was creative, they were different."

Shearer co-created, co-wrote and co-starred in Rob Reiner's 1984 film This Is Spinal Tap with Michael McKean and Christopher Guest; the three of them also collaborated on the acclaimed 2003 spoof A Mighty Wind, which was written by Guest and Eugene Levy, and directed by Guest.

Shearer's television work also includes two specials for Cinemax, "It's Just TV", and "This Week Indoors" (co-created with Merrill Markoe) and "The Magic of Live". He directed the entire six-episode cable series, "The History of White People in America", co-created by Martin Mull and Allen Rucker, as well as the two-hour feature finale of the series, "Portrait of a White Marriage". He also co-wrote and directed Paul Shaffer's fantasy special for HBO, "Viva Shaf Vegas" (with Shaffer and Tom Leopold). His first theatrical feature, which he wrote and directed, was "Teddy Bears' Picnic", a dark comedy loosely based on the workings of Bohemian Grove, the secret retreat of the elite.

Shearer has two books published, "Man Bites Town" (a collection of his Los Angeles Times Magazine columns) and "It's the Stupidity, Stupid". As of 2005, he is finishing work on a comic novel about Native Americans and gambling called "Not Enough Indians".

Shearer is probably best known for his prolific work as a voice actor on The Simpsons (1989 to date), where he does the voices of Mr. Burns, Waylon Smithers, Ned Flanders, Reverend Timothy Lovejoy, Kent Brockman, Dr. Julius Hibbert, and Principal Seymour Skinner, among others. He was one of three Simpsons vocalists to guest star on the show Friends; the other two were Dan Castellaneta and Hank Azaria.

Since 1983 Shearer has been the host of the public radio comedy/music program Le Show on Santa Monica NPR affiliated radio station KCRW. The show is podcast and airs on public radio stations throughout the country. He is the regular announcer for TV Land and, since mid-2004, for KIRO-AM radio in Seattle. Since May 2005 he's been a contributing blogger at The Huffington Post. Shearer has homes in both Santa Monica, California and the French Quarter of New Orleans, Louisiana. According to a telephone call on Ask Mr. KABC, his house survived Hurricane Katrina and he is alive and well.

Since 1993, Shearer has been married to singer-songwriter Judith Owen.