He is the creator of the iconic underground characters The Fabulous Furry Freak Brothers, Fat Freddy's Cat, and Wonder Wart-Hog.

[3] Directly after graduation, Shelton moved to New York City and got a job editing automotive magazines, where he would sneak his drawings into print.

He applied for a job at the Cleveland-based American Greeting Card Company (where a fellow underground comic artist Robert Crumb had worked) but was turned down.

[7] Then Shelton became art director for the Vulcan Gas Company, a rock music venue in Austin, Texas, where he worked with Jim Franklin.

[citation needed] Also in 1968 Shelton self-published Feds 'n' Heads, a collection of strips first published in the Austin underground paper The Rag.

[8] In 1969, Shelton co-founded Rip Off Press with three fellow "expatriate" Texans: Fred Todd, Dave Moriaty, and cartoonist Jack Jackson.

During this period, Shelton was also a regular contributor to Zap Comix and other underground titles, including Bijou Funnies, Yellow Dog, Arcade, The Rip Off Review of Western Culture, and Anarchy Comics.

In 1979, Universal Studios paid Shelton and Rip Off Press $250,000 for the rights to make a live-action Fabulous Furry Freak Brothers film.

"[13] It was reported that Universal's acquisition of the Freak Brothers film rights in 1979 was in order to prevent competition against the Cheech & Chong franchise.

[14][13] At one point, the Freak Brothers' antics were reportedly being turned into a Broadway musical [citation needed] after a stop motion animated film, titled Grass Roots and produced by Celluloid Dreams,[15][12][16] fell through.

Finally, in 2021, an animated series called Freak Brothers featuring the voices of Pete Davidson, John Goodman and Woody Harrelson, premiered on the streaming service Tubi.