An animated enemy is a character which changed with the setting of the game board, and "attacked" Mikey, causing the team that moved Mikey that gets run over by an enemy to lose control to the opposing team. The Enemies included:
- A Ghost would scare Mikey away in Creepyville.
- A Witch Doctor in the Volcano Jungle, who would blow up a voodoo doll of Mikey and then let it fly off and deflate.
- A Fire-Breathing Dragon in the medieval realm Camelittle, who would burn Mikey by breathing fire on him with a yelp and flying off screen.
- A Hammerhead Shark, found in the Specific Ocean, who would flatten Mikey with his hammerhead, turning Mikey into a coin with his face on it. The Hammerhead Shark also appeared in the underwater areas of Pirate's Cove.
- Blackboard the Pirate, a pirate shaped like a chalkboard, found in Pirate's Cove, who would attack Mikey with a ruler sword by saying "Walk the plank, ye scallywag!"
- Silly the Kid, a baby armed with baby-bottle pistols in Slurpy Gulch who would say "Dance, pardner!,” then loses his balance from the effort and falls; a spoof of Billy the Kid.
- Game Over the town bully in Mikey's Neighborhood who would say, "Hold it right there, bean brain!" and hit Mikey in the face with a cream pie. Game Over also appeared in the WeGot'Em Mall, the Time Portal, and on the beach in the Specific Ocean.
- Two Giant Smooch Aliens, creatures with pigtail wigs and big lips, found in Cape Cosmos, that would surround Mikey, kissing him until he became dizzy and powerless.
- A Djinni in the Forgotten Desert who would cast a spell on Mikey, turning him into a chicken. He reappeared in the Enchanted Flight stage of the Video Zone in Season 2, casting lightning bolts on the player.