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 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 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.

Red and Blue's default names in the game's coding are Ninten and Sony, respectively, a reference to Nintendo's rivalry with Sony in the gaming industry, i.e. the Playstation vs. the N64.

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.

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.

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.

After Shigeru Miyamoto became Satoshi Tajiri's mentor, Satoshi gave thanks to him by making the default rival name 'Shigeru'. Satoshi made himself the default name for the protagonist. This can be found in the Japanese Generation I Pokemon games.

Some Pokemon share the same cries. Some examples are Charizard and Rhyhorn, Ditto and Poliwag, and Goldeen and Caterpie.

Drowzee's sprite has five fingers. It is supposed to have three.

The Spanish translation of the first generation Pokémon games is known for being very poor quality with many translation errors. One of the most remarkable mistakes is the translation of the move "Slam" into "Portazo", which actually means "Door Slam". This name remains even in the latest games (5th Generation).

The article "the" is used when announcing trainers for battle (for example, Charlie the Bug Catcher. It worked for typical trainers but not Gym Leaders, Elite Four, your rival, or link battles. A screenshot in the instruction manual of the English Red and Blue still contains the text "The Brock wants to fight!", possibly suggesting a late removal. The instruction manual also calls them Pokemon Leaders, instead of Gym Leaders.

Kingler's front-facing sprite erroneously depicts its claws as equal in size, when in reality the right claw is actually much smaller than the left.
Strangely enough, in the original Japanese Red and Green versions, the claws are their correct sizes. The claws are once again their correct sizes in Yellow version.
Additionally, the side that the larger claw appears on was changed after Generation I. The bigger claw became the left claw while the smaller claw became the right.

There's a mistake on Cloyster's sprite. It shows its shell positioned horizontally instead of vertically.

The blurb on the back of the boxes states that 139 different Pokémon can be obtained in each game without trading. This, however, includes all Pokémon that the player must choose between (i.e., both the Omanyte and Kabuto families are counted). Therefore, the true total of different Pokémon obtainable in one adventure without trading is 124, which excludes the two unchosen starter families, one Fossil family, two Eeveelutions, one of Hitmonlee and Hitmonchan, and the four Pokémon that only evolve when traded.

The old man, who is laid down protesting his lack of a morning coffee in the localized version, is actually passed out from drunkenness in the Japanese version. You would have to bring him coffee in order to sober him up.

There is a glitch where the player can fish in large statues found in gyms and Indigo Plateau, even being able to catch Pokemon. You can find Magikarps with the Old Rod, Poliwags and Goldeens with the Good Rod, and Krabbies, Psyducks, and Goldeens with the Super Rod. The Super Rod only works in the Cerulean City gym. You can also surf on these large statues, but no Pokemon will appear while surfing.