Shortly after the game's release, a screenshot started circulating online depicting the Seagallop ferryman in Vermilion City telling the player: "By the way: if you like this game, buy it or die." Those who posted the screenshot claimed that it was a hidden message which was only triggered if the game detected that it was running a pirated copy. This claim appeared to be further corroborated by people claiming that they had encountered the message themselves when playing the game with unofficial Game Boy Advance emulators or when hacking legitimate cartridges with cheat devices, and attracted further popularity after being disseminated by various gaming YouTubers.

However, while the screenshot was not photoshopped, the claim that it was an anti-piracy measure was not true. Rather, the text was added into the game's code by an anonymous individual who distributed a ROM of it online; the claim that it was an anti-piracy feature was most likely used by the individual to circumvent ROM distribution sites' restrictions on modified games. This explains why anecdotal reports of encountering the text were so much higher than what would be expected from a complete hoax, as well as why the text is absent when examining an unaltered ROM of the game in a hex editor.

From the start of the game, if you make it up to after the first Rival Battle when you are about to leave Pallet Town without opening the Start menu once, an NPC will appear in front of the town's exit who will interrupt you if you try to leave and recite the Trainer's Tips sign that teaches you how to save your game.

The Pokedex will incorrectly display A Pokemon's category; only showing the first word of a Pokemon's category. For example:

All other games in the Pokemon series categorize Squirtle as the "tiny turtle Pokemon". In the Pokemon Fire Red & Leaf Green Pokedex, Squirtle is listed as the "Tiny Pokemon".

Despite the Pokemon Mansion on Cinnabar Island only having one entrance, the mansion has two exits and both will transfer the player to the front door.

Once the player completes the main storyline and obtains the National Pokedex, Entei, Raikou and Suicune become available to capture as roaming legendaries. During an encounter with one of them, if the player uses Mean Look and one of the legendary dogs uses Roar, it will end the battle as usual. However, the Pokemon will have disappeared from the map upon checking the Pokedex to locate the Pokemon, making it impossible to further encounter them in that save file.

In the Sevii Islands is a large patch of grass with paths running through it called 'Pattern Bush'. It's thought these patterns were made to resemble the circuit board of the original Red and Green games. Fittingly enough, the grass there only contains bug Pokemon, referencing all the "bugs" (as in glitches) found in the original games.

In the Pewter City Museum, in the space exhibit on the first floor, is a man who speaks about the date July 20 1969, and that humankind first stepped on the moon. This is an actual reference of the moon landing of the Apollo 11, and Neil Armstrong and Buzz Aldrin to be the first people to walk on the moon on July 20 1969.

The original Red and Green Versions were supposed to have a female trainer along with the male trainers, Red and Blue. She was most likely removed due to hardware restrictions, but is still seen on the official strategy guide and artwork. The character was used as the character 'Green' in the comic and 'Leaf' in the remake, FireRed and LeafGreen.

Since the games run on the same engine as the Ruby and Sapphire (and, by extension, Emerald) games, the same weather effects are also in the data for both versions. These include Cloudy, Rain, Snow, Thunderstorm, Sandstorm, Volcanic Ash, Mist and even a texture for Underwater. Except for the cloudy and Mist weather effects, all others are unused.

The two passwords required for entering the Rocket Warehouse on Five Island are "Goldeen need log" and "Yes nah Chansey". Both of these are actually palindromes - they read the same backwards as they do forwards.

The reason that LeafGreen is the intentional release instead of WaterBlue is that Junichi Masuda, the game director, wanted an icon of peace (which is what leaf is said to represent) instead of an icon that conflicts with the image of fire used by the other game.

When playing as the male hero, a movie about four boys walking down railroad tracks is playing on the television downstairs, likely referencing the film Stand by Me. If playing as the female hero, a movie about a girl in pigtails walking down a yellow brick road is playing, likely a reference to the film The Wizard of Oz.

In Japanese versions of the game, the player's bedroom has a Famicom. In the US game, this has been changed to a front-loader NES.

In Pokémon Red, Blue, and Yellow, as well as their remakes FireRed and LeafGreen, a truck was placed in the S.S. Anne's port. The truck seems to serve no purpose. Its presence in the remakes could be a reference to the original rumors that Mew could be found under the truck.