Grayson is probably most famous for his role of Joey Wheeler (Katsuya Jonouchi in the English manga and Japanese versions) in the English-language version of the second series Yu-Gi-Oh anime (known as Yu-Gi-Oh! Duel Monsters in Japan). He also provides the voice of Teenage Mutant Ninja Turtles character Michelangelo. He was also Phibrizzo in Slayers Next
On his choice of Wayne Grayson for this role, Lloyd Goldfine said:
When trying to decide who should play Michelangelo and who should play Donatello, I kept switching those parts between Sam Riegel and Wayne Grayson; one day Sam would play Mike and Wayne would be Don, but then I'd hear them messing around in the recording booth, doing each other's lines, and I'd think, "Hey... that sounds really good!" and so I'd switch 'em! I couldn't make up my mind! But finally it all crystallized; Sam became Don and Wayne became Mikey.