The anime was greenlit after the Pokémon manga serialized in CoroCoro Comic proved popular; Shogakukan's Masakazu Kubo pushed for a TV adaptation with support from Nintendo's Takeshi Kawaguchi and Creatures' Tsunekazu Ishihara, leading Nintendo to grant animation rights.

Although in the games players first choose between Charmander, Bulbasaur, and Squirtle, the anime's producers chose Pikachu as Ash's starting partner instead, wanting to broaden the show's appeal to include girls as viewers.

The names Satoshi (Ash) and Shigeru (Gary) were taken from Pokémon creator Satoshi Tajiri and Nintendo designer Shigeru Miyamoto respectively.

According to writer Shoji Yonemura, Team Rocket's trio of Jessie, James and Meowth was strongly influenced by the villainous trio archetype from the Time Bokan series.

In some episodes Team Rocket's mechs have been depicted using Nintendo's Wii Remote and Nunchuk controllers as parody references; these gags were sometimes replaced in international versions.

The infamous "Dennō Senshi Porygon" episode broadcast on December 16, 1997 triggered the mass photosensitive-epilepsy incident known as the "Pokémon Shock," causing the series to go on hiatus for over four months before resuming.

The show's highest-ever household rating in the Kanto region was 18.6%, recorded for episode 33, "The Fire-type Pokémon Grand Race!!", broadcast November 11, 1997.

The first Pokémon film, Mewtwo Strikes Back, released in Japan in 1998, became the fourth highest-grossing film in Japan that year with box office revenue of 7.24 billion yen.

The narration for the Japanese series was performed by Unshō Ishizuka from the very first episode through Sun & Moon episode 91; after his death, Kenyu Horiuchi took over from episode 95.

Pokémon has aired in 192 countries and regions as of March 2024, and is considered one of the most successful video game adaptations of all time, with over 1,300 episodes produced.

Feedback from the anime later influenced the games themselves: Pikachu could only learn Thunderbolt via TM in the original Red/Green/Blue games, but starting with Pikachu Version it could learn the move by leveling up, reflecting its signature anime move; likewise, from X & Y onward, Pikachu's in-game cry uses the same voice actress, Ikue Ōtani, as in the anime.