Mary Beth is a famous cosmetics spokeswoman who engages in a romantic relationship with Cosgrove, Freakazoid's best friend. Freakazoid finds out about the relationship when he sees Cosgrove and Mary Beth dancing together; which made him feel better about Cosgrove not being able to hang out with him, because he was happy that Cosgrove has someone. However, Mary Beth is seen by Freakazoid transforming into an evil green monster after bumping into a waiter, and she threatened his life and tossed him towards a wall.
Cosgrove refused to believe Freakazoid when he tells him about Mary Beth's evil secret, and it is at that moment that Mary Beth encountered both of them and invited her to dinner at her place. That night, Freakazoid attempted to out Mary Beth by getting her to light a candle with her nose (which only monsters can do), and it is at that moment that Cosgrove tells Mary Beth about Freakazoid's accusations. All three of them laugh it off, but Mary Beth does confess to being a monster and transforms again, this time imprisoning Freakazoid.
Mary Beth's plan was to siphon Freakazoid's essence and ingest it to maintain her youth and immortality; something she has done for eons. She hooked Freakazoid in a machine that was doing just that, which was causing Freakazoid to ramble and become weak. Mary Beth stated that she wanted to share the essence with Cosgrove so they could live together forever, but Cosgrove refused to endanger his best friend, so Mary Beth put him in the machine with Freakazoid. At that moment, Mary Beth began to age; telling herself to hold on until her twisted plan is completed. Thanks to Cosgrove urging the audience to applaud, Freakazoid regains his strength and frees himself and Cosgrove, while the evil Mary Beth rapidly aged away to dust.
- Tress MacNeille voiced Mary Beth in her human form. In her monstrous form, she was voiced by Frank Welker.
- Tress MacNeille is also known for voicing the evil Hama from Avatar: The Last Airbender, vampiress Norma Deathman from The New Scooby-Doo Mysteries, evil conspirator Dame Judith Underdunk from The Simpsons, and the greedy Jeweler's Wife from Timon & Pumbaa.