Much as with the Beetlejuice cartoon before it, The Mask: Animated Series took many elements from the source movie but dropped characters and changed certain other persona. Reporter Peggy Brandt (Amy Yasbeck's character from the movie) is the main female character in the show. Tina Carlyle (Cameron Diaz's character in the movie) is absent from the cartoon. However, the events of the movie are alluded to, as Charlie knows that Stanley was the Mask (though thinks Stanley threw it away), and Stanley is still upset over Peggy selling him out to the mob (given that Stanley and Peggy were never treated as a potential couple, there may have remained some bad feelings over that though The Mask himself sometimes tries to woo her). A gypsy named Madam Suspiria at one point claims that the Mask is the most powerful artifact in the world when she remarks "The most powerful artifact in the world and this idiot keeps it with his laundry". Unlike in the movie, Ipkiss is able to use the mask in daytime as well as at night.
Niko and Dorian Tyrell, the two primary antagonists of the 1994 film who died during the course of it, do not appear in the animated series. However, an early draft of one episode was to have the ghosts of Niko, Tyrell and their deceased henchmen to return to Edge City and wreak havoc. The plot was to involve both of the ghosts and their gangs to break the remaining gang members out of jail, regain their areas of influence and resume their war against one another. However, the script would determine that they join forces in an effort to exact revenge against Ipkiss. Both Matacena and Greene were approached in order to reprise their roles, but eventually the episode was scrapped.
The cartoon, despite having a "realistic" setting in the fictional town of Edge City, often relies more on Tex Avery-style humor and on occasion, breaks any meaningful laws of reality; one episode featured the Goofalotatots, parodies of the Animaniacs, treating them as if they were naturally alive. Another featured the Mask becoming a personal assistant to the President of the US, with the job merely handed to him (the president was a caricature of no real president; it should also be noted that former Mask comic writer John Arcudi wrote both example episodes, a stark departure from his usual writing). Police officers are portrayed as idiots who can't see even obvious clues.
Also continued from the movie was the consistent visiting by The Mask of the Coco Bongo; a fictional, glamorous night club frequented by the Edge City well-to-do, which was based on the Copacabana in New York City. In the episode "A Comedy of Eras", in which Dr. Chronos manipulates time so that the future Edge City becomes a corrupted, Nineteen Eighty-Four-like dictatorial society ruled by the villainess, features a Coco Bongo which has been destroyed – a development that horrifies and enrages The Mask and provides him with the motivation to ultimately defeat Dr. Chronos.
During the late nineties, Rob Paulsen appeared on US TV talk show, Donny & Marie. When talking about his role as Stanley Ipkiss/The Mask, Rob said "I'd get to be Jim Carrey for a whole lot less cake".