Harmonquest was born from a segment on the podcast Harmontown in which the cast would play the fantasy RPG Pathfinder. Game master Spencer was originally an audience member who became a regular on the podcast after volunteering to DM the segment.
Harmonquest star and co-creator Dan Harmon was an active player of role-playing games in his youth which was a big motivating factor in making the show. Community (2009), another Harmon creation, features the rpg Dungeons & Dragons prominently in two episodes.
While they claim to use Pathfinder as a basis for the game system, they ignore a massive amount of the rules regarding turn order/initiative and other mechanics of the game - rules which might distract from the improvisational nature of the show and would take significantly longer to explain to their guests unfamiliar with tabletop gaming such as D&D or Pathfinder.
The show shares many elements with its forerunner 'live D&D' podcast segment including the fantasy setting, the core cast of Dan Harmon, Jeff B. Davis and Erin Mcgathy and the use of short-lived guest characters. However Harmonquest is an entirely new story with new characters and no continuity from the original tale
Guest star Gillian Jacobs also appeared in another Dan Harmon show, Community (2009), in which her character plays a tabletop role playing game.