Mr. Mime was conceived and developed by Ken Sugimori for the first generation of Pocket Monsters games Red and Green, known outside of Japan as Pokémon Red and Blue. Its name originates from its appearance and hobby, that of a mime. Mr. Mime can be a female because its Japanese name didn't involve Mr. or Ms. Appearing as an anthropomorphic creature, it has a pink head with red cheeks and blue, frizzy hair, a round, white body with a red spot in the middle, light-pink arms and legs are connected to its body by red spheres, white, five-fingered hands, and black feet that curl upward at the tips. Their hands are depicted with four fingers and an opposable thumb, with larger fingertips and red dots on their underside. However, game representations of the character featured only three fingers on each hand until the release of Pokémon Ruby and Sapphire. Despite their localized name, any one Mr. Mime can be either male or female.
Mr. Mime can have the ability Soundproof or the ability Filter. Soundproof causes Mr. Mime to be immune to sound-based moves. Filter causes all super-effective moves that hit Mr. Mime to be weakened. Mr. Mime are gifted with the art of miming at a young age, but as they mature, they gain the ability to make invisible objects by emitting energy from their fingers and minutely vibrating their fingertips to harden the air around them and form a wall. Barriers generated this way can repel harsh attacks, and its gestures and motions can convince watchers that something unseeable actually exists; once this is achieved, the perceived item will materialize. Mr. Mime are very prideful of their pantomime acts, and will heavily slap anyone that interrupts them while miming.
Delia Ketchum obtains a Mr. Mime in the Episode Mr. Mime Time!. She first mistook Mr. Mime for Ash Ketchum, because Ash was dressed in a Mr. Mime outfit. She nicknamed the Mr. Mime 'Mimey', rendering him as one of the few Pokémon that is ever nicknamed in the anime. Mr. Mime has appeared with her ever since, helping her around the house.