In a 1997 interview with Famimaga 64, Satoshi Tajiri said that the Pokémon Porygon was made due to people saying that he should develop a 3D game instead of a sprite-based game on the Game Boy:

In 2020, an unreleased extended cut of the 1998 Pokémon Generation I bus commercial was uploaded to YouTube. This extended cut shows that the bus featured in the advert was actually crushed during production, despite the final commercial cutting from the compactor starting to the compactor having already crushed the bus. The unreleased crushing scenes do not have Pokémon superimposed into the windows.

In an interview with Junichi Masuda, he stated that the source data for the game was almost lost because the computer that stored the data suffered from a nasty crash.

In an interview with Yomiuri Online, Pokemon designer Atsuko Nishida revealed that the reason why Pikachu was made a rare encounter in Viridian Forest was because of her own personal favoritism towards the character and what she described as a feeling of "not wanting to let other people have Pikachu."

In the Pokemon Origins anime miniseries, Red uses a Charizard, Dodrio, Persian, Scyther, Lapras and Jolteon during his fight against Blue at the Indigo Pleateau. These were the same Pokemon on the team used by creator Satoshi Tajiri during his test playthrough of Pokemon Red & Blue.

The 7th gym leader originally had a different design. Because of its similarities to early artwork to Blaine, as well as his appearance in the anime, this design is likely the original design for Blaine.

Ken Sugimori revealed on his Twitter that Brock was originally meant to be the second Gym Leader, with what looks like a Youngster being the original first Gym Leader.

On route 10, picnicker Coral says "The Pokemon here are so chunky! There should be a pink one with a floral pattern." This description perfectly matches the Pokemon Munna, from Pokemon Black & White released twelve years later.

Promotional material for the game lists Paras with the name "Parasyte". This name may have been changed in order to avoid copyright issues with the 1990 manga series, Parasyte.

It's possible to initiate a glitch that allows the player to walk through walls by use of the Safari Zone's limited steps, and having a poisoned Pokémon. By having the game think that you're still within the Safari zone while outside, and jumping over a ledge on the 500th step, the game will send the player back to the entrance of the Safari Zone while still having it within its data that they are currently mid-jump. When exiting a building with this glitch active, the game will crash, but it's possible to exit the entrance room of the Safari Zone by having the player's Pokémon die of poison. Using this glitch allows the player to skip certain sections of the game, but is riddled with a number of limitations.

The front and back pages of Satoshi Tajiri's book "New Game Design", features what appear to be pre-release sprites from Pokemon Red and Green.

The infamous Missingno glitch can be triggered by the player having Pokemon knowing the moves "Fly" and "Surf", going to Viridian City and triggering the Old Man's catching tutorial. Afterwards the player must Fly immediately to Cinnabar Island and surf along its eastern coastline without moving away from it or back onto the island itself, eventually triggering an encounter with Missingno (Or a similar glitch Pokemon named 'M), after which the item in the player's 6th Item slot will be duplicated to a maximum of 255.

This glitch is triggered by the game's internal data replacing the player's chosen name with the "Old Man" string for the sake of the tutorial and it not being properly replaced by another battle. Whatever letters are used in the player's name will also change what form Missingno will take. For example, a W being used as the 3rd, 5th or 7th letter will trigger the Kabutops Skeleton Form Missingno, an X will trigger the Aerodactyl Skeleton Form and a Y will trigger its Lavender Tower Ghost Form.

The Route 24/25 theme has a strong resemblance to the Sky Theme from Mario & Wario, a Japanese-only Super Nintendo game which was also developed by Game Freak.

In the Pokemon Red and Blue beta, Cubone was originally known as "Orphon," a corruption of the word "orphan," based on its abandonment at birth.

There are only 37 unique sounds for all 151 Pokémon cries. Effects such as modifying the speed and pitch are applied to those 37 base sounds to make the different cries for each Pokémon.

Lance's Dragonite knows barrier, a move which Dragonite cannot learn through legitimate methods.

Prior to release, the game was rejected multiple times by Nintendo until Shigeru Miyamoto took interest. When Game Freak wanted to start development, they required funding, and thus the team worked on smaller Nintendo projects to obtain funding.

On Cinnabar Island if you don't have the key to the gym with you there is a small glitch you can perform. First, use Surf on the right hand side of the island and move upwards until you're across from the door. Get off your Pokemon and walk until you're in front of the gym door where you'll get the message about it being locked. Look up and you'll see an old man on the roof while this text is displayed.

Indigo Plateau's background music sounds very similar to the Mother 1 (EarthBound Beginnings) Mt. Itoi theme.

The international versions of Red & Blue are based on the Japanese version of Blue. Many changes were made in this version, including updated graphics and sound, as well as several bugfixes found in the Japanese versions of Red & Green.