The Animated Series features the main characters, setting and basic premise as the movie. However the show differs from the movie in many ways, due to the additional freedom animation provides, as well as the language and content restrictions that broadcast TV demands. For example, the characters of Jay and Silent Bob were changed from drug dealers to mischief makers (selling firecrackers instead of marijuana), and the explicit sexual dialogue in the film (which was enough to initially achieve an NC-17 rating in the US) is almost completely erased. The series also introduced a new villain, Leonardo Leonardo, after whom Leonardo, New Jersey is named, the town in which the series and the film, takes place.

The show has a pace quite different from the film (more in line, perhaps, with the frenetic pace of Smith films like Mallrats and Jay and Silent Bob Strike Back), and the creators regularly play around with the medium, parodying different plot devices. For example, the second episode is a clip show, a common format for long running sit-coms where the characters reflect on previous events from the show and the majority of the show is archive footage. There is a long sequence of scenes — several of which are nested multiple levels into each other — that look back on previous episodes (and the episode itself), even though only a single episode had been produced before that one, and so most of the "clips" were actually original material created solely for the joke of the clips themselves.

As with the film, most of the characters are either cynically irresponsible or completely crazy, with Dante being the only really sympathetic "normal guy" around. As a result, Dante is usually the straight man to the hijinks of the other characters. Indeed, Dante seems to be the more intelligent one of the duo most of the time, in contrast to the film - the humor is essentially the same, but Randal's sarcasm, irony and witticisms are played as idiocy.

Besides the original voices of the film characters and Baldwin, the show sported an impressive list of guest performers. Gwyneth Paltrow, Charles Barkley (who appeared in five out of six episodes of the series, making him an unofficial cast member on the show), Grant Hill, Reggie Miller and Dan Patrick playing themselves as well as Gilbert Gottfried playing Patrick Swayze and Jerry Seinfeld, Michael McKean playing Professor Ram and The Creepy Guy, Kevin McDonald playing Batman Fan in Episode 6, Julia Sweeney playing the mom in Episode 6, Al Franken playing the Mayor of Leonardo, James Woods playing Major Baklava and Judge Reinhold playing a Judge version of himself. Walt Flanagan and Bryan Johnson voice Walt Grover the Fanboy and Steve-Dave Pulasti respectively, two characters they have repeatedly portrayed in Kevin Smith's films, in a number of episodes.

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