Although Prismatology, along with his book Emetics, was first mentioned in Culture Shock, Hugh Bliss did not appear in person until Situation: Comedy as a celebrity guest host for WARP's game show "Who's Never Going to be a Millionaire". There he showed off some of his tricks, such as his mind reading and ability to change colors, which Sam and Max exploited in order to meet one of the requirements needed to get into Myra Stump's show. While Sam was skeptical, Max presented himself as Hugh's greatest fan, a fact which, suspiciously, did not disturb Hugh in the slightest.
Hugh would pop up again in Abe Lincoln Must Die! where he reopened the otherwise perpetually closed Esperanto Bookstore, which he was using to sell copies of his book Emetics, as well as to spread the word about Prismatology. There he showed Sam and Max another of his tricks, disappearing, giving Sam the opportunity to steal his advertising sign (Free home delivery) which they later used to secure Max's election as President of the United States.
Hugh did not appear in Reality 2.0. However, once inside the titular virtual reality simulation, Sam and Max encountered a virtual representation of him in the form of the Internet Wizard, which went on to give them a rainbow kit for their virtual car as well as tell them their future. However, after defeating the Internet, Sam and Max had become aware of a menacing figure by the name of Roy G. Biv, who was behind the Reality 2.0 scheme and, by extension, the other cases involving hypnotism that had defined the season. As Sam and Max were left to ponder the true identity of the villain, the camera panned up, revealing The Moon with Hugh's face superimposed on it!
Finally, in Bright Side of the Moon, Sam managed to figure out the true identity of Roy G. Biv: Hugh Bliss himself (using a deduction that had nothing to do with Roy G. Biv being an acronym of the colors of the rainbow; red, orange, yellow, green, blue, indigo and violet; which would have been the obvious clue, and instead some obscure tidbit about how Hugh never said "Morning"); spurring the Freelance Police to infiltrate Hugh's Private Prismatology Retreat on The Moon. Once they confronted him, however, Hugh explained his master plan; to hypnotize every man, woman and child into a version of himself. Explaining that only Max's chaotic power was capable of ruining his plan, Hugh proceeded to "Separate his bliss", which turned out to involve relieving Max of his right hand, stomach and tail thus depriving him of his anger, gluttony and sloth, respectively. A side effect of this procedure resulted in the creation of three additional Maxes, each possessing one of the originals body part and thus embodying the accompanying vice. By defeating each of these and reacquiring their body parts, Sam managed to bring Max back to himself in time for their final confrontation with Hugh Bliss. Returning to his inner sanctum, Max managed to remove Hugh from his mind control apparatus. It was at this time that Hugh Bliss revealed his true nature, an extra-terrestrial colony of bacteria that fed off the endorphins generated when an organism experienced bliss. Essentially, his whole motive was to force the entire earth into a state of true bliss to ensure a limitless food source for himself. With Max trapped in the mind control machine, Hugh put Sam through a series of easily escapable death traps. Fortunately, with the help of a few artifacts he had acquired along the way, Sam managed to outwit and eventually trap Hugh in a dunking booth which he then heated up with a lunar lander engine, effectively pasteurizing the villain to death and thus ending his threat to earth for good.
During Season Two, Hugh Bliss could be found in Sam and Max's trophy closet in their office, or at least what was left of him after being boiled down, ingested, and passed through the digestive system of our favorite lagomorph. They would finally meet up with him again in What's new, Beelzebub?, where his immortal soul had been employed as a censor in Hell.