Clefairy debuted in the first chapter, Introducing the Pokémon Clefairy!! where he was a wild Pokémon living in a field. Red, racing to get to Professor Oak's lab before his rival Green does, decides to take this field as a shortcut where he finds a wild Nidoran♂ and the Clefairy who attempt to attack him. Clefairy drops some coconuts on Red from a tree above, only to shortly fall off and drop onto the Nidoran♂, knocking him out. Red thanks Clefairy for the help and continues to run for the lab, finding that Green had already made it there. While the three discuss about Professor Oak's favor of completing the Pokédex, Clefairy bursts into the lab and is yelled at by the professor. When given the choice of which starter Pokémon he wants, Red decides to take Clefairy with him, which thrills the Pokémon greatly. Green is however skeptical that Red can be a successful Trainer with a Clefairy, and has his chosen starter Pokémon Charmander attack the Clefairy, setting his tail on fire and causing the Pokémon to run around frantically, which sets the entire lab on fire and enrages Professor Oak.
In Bring Down the Powerful Opponent Onix!!, Red attempts to challenge the Gym Leader In the Pokémon Pocket Monsters manga in a battle, but Clefairy flees after seeing his Onix shortly after witnessing Green and his Charmander being thrown out the Gym, which forces Red to drag Clefairy back. Inside, the two learn of Brock's Pokémon collection, and find out that Clefairy's cousin Pikachu is also a part of it. This angers Clefairy and gives him the courage to fight Brock's Onix in a battle, which Clefairy prolongs by using an assortment of tricks. Clefairy later manages to defeat Onix by drawing his picture onto its tail, causing Onix to chase its tail until it becomes dizzy, and becomes knocked out after Clefairy smashes a fallen pillar on its head. By winning the battle, Clefairy's cousin is freed from Brock's collection and joins Red's team.
Clefairy evolved into a Clefable in Clefairy Evolves... At Last?!, but had later devolved back into a Clefairy in the same chapter.
Clefairy has continued to travel with Red in Johto, Hoenn, Sinnoh, and Unova.
Clefairy is often an unintelligent, lazy, loudmouthed, crass, vulgar, and generally rude Pokémon. He is typically selfish, often thinking about himself instead of others, and is also cowardly, preferring to win battles through the use of trickery, luck or other unconventional means. More often though he will try to flee and hide, sometimes even going as far as to disguise himself, to avoid battling others, especially against Pokémon who are by far larger and stronger than he. Clefairy does occasionally show some redeeming qualities, but he is usually a mischief maker most of the time. His manners and stupidity are often an annoyance to Red and the rest of his Pokémon team, and is also especially a major cause in fights between Pikachu and Tyrogue, who are both smarter, more well-behaved and otherwise more capable than Clefairy.
His mannerisms are also well known among Pokémon across entire regions, who typically refer to Clefairy as "that blockhead Clefairy". Rather than taking offense to this, Clefairy falsely believes it to be a compliment with the idea that he is "famous" among Pokémon.