Pehl was one of the writers on the MST3K series. From 1992 to 1996, Pehl played the role of "Magic Voice", a disembodied woman's voice who would announce upcoming commercials at the beginning of the show. In 1996, she began playing the role of Pearl Forrester, the mother of Dr. Clayton Forrester (Trace Beaulieu), initially as a guest character and then as a recurring character on the departure of TV's Frank (played by Frank Conniff). When Beaulieu left the series at the end of the seventh season, she took over as the head "mad" on the series. Pehl also played a number of other small roles on the series, such as "Jan in the Pan", a woman's head that had been removed from a body (inspired by the movie The Brain That Wouldn't Die).

Since the ending of the series, Pehl has had comedy segments on National Public Radio.

Pehl turned her hand to writing in 2004 with her first book I Lived With My Parents and Other Tales of Terror published by Plan 9 Publishing.

Pehl has stated that she is a Catholic, and has written for the Catholic Digest, including an article about a priest who works in a circus.

In 2007, she returned to MST3K-style riffing on bad movies, joining former castmate Mike Nelson's RiffTrax for the film Glitter, and Bill Corbett for The X-Files movie, as well as becoming a cast member on Joel Hodgson's Cinematic Titanic, making her one of a select few MST3K alumni to be involved with both Mike and Joel's successor projects. After an extended stay in New York City, she now resides in Austin, Texas with her husband Mary Jo Pehl's Homepage, and performs with the Violet Crown Radio Players. In October 2007, she recorded an interview with the Austin-based podcast Chicken Fried Radio. To date, hers is the only interview the show has aired.

She has since starred in the upcoming science fiction computer game DARKSTAR - The Interactive Movie as both Captain Beth Ingram of the Starship Bridgebuilder and the voice of the computer Westwick Main.

On October 30, 2007, Joel Hodgson announced he was starting a new show with the same "riffing on bad movies" premise as MST3K called Cinematic Titanic, together with former MST3K cast and crew members Pehl, Trace Beaulieu, J. Elvis Weinstein, and Frank Conniff. Cinematic Titanic - Homepage of MST3K alumni Joel Hodgson, Frank Conniff, Josh Weinstein, Trace Beaulieu and Mary Jo Pehl

As of November 2009, she continues to tour with Cinematic Titanic.