According to Weird Al Yankovic, when the show was hiring writers, Seth MacFarlane approached the network with the original blueprints for Family Guy, hoping to turn it into a series of animated segments for the show. Had he been hired, The Weird Al Show would have been to Family Guy what The Tracy Ullman Show was to The Simpsons.
The show's theme song contains the lyrics, "Well, the very next year he met a dental hygienist with a spatula tattooed on her arm." This is a double reference to UHF (1989) where Al's girlfriend was a dental hygienist played, and in which a "Spatula City" skit/ad also appears.
New FCC regulations required a portion of children's programming to be educational, therefore CBS executives required each episode of the Weird Al show to have some kind of "moral lesson" at the beginning that was played out during the show.