Based on the Domino's Pizza floppy-eared mascot, Yo! Noid puts you in control of the buck-toothed pizza eater. New York is under attack by a Noid look-alike called Mr. Green and his many flunkies. As the real Noid, armed with a killer yo-yo, your job is to cruise the city while avoiding traps and obstacles and take down do-badders (such as pirates, hooligans, and dive bombers) with your "shoot the moon" yo-yo trick.

For an added boost, Noid can grab scrolls that give him magical powers such as smart bombs and the ability to freeze the action. Also, there are incredible inventions which enable Noid to maneuver in certain parts of the game. These inventions include a HyperBoard (which is similar to a skateboard), a Pizza Crusher (which is like a pogo stick), and an Ornithopter (a one-man flying machine).

The action takes place all over New York City, including Central Park, the Bronx, on the rooftops of skyscrapers, in the skies, and on the wharf. After each odd-numbered level of play, Noid must enter a pizza-eating contest, which is basically a bonus round.