The main difference between Red and Blue are the differences in the Pokémon available. Each game has a bunch of exclusive Pokémon which forces players to trade between one another to complete their Pokédex. Pokémon Yellow has a bit of overlap in both games but still has a number of the pocket monsters that cannot be captured. You can check out each game’s list of exclusive Pokémon here.
In addition to each game’s list of exclusive monsters, Yellow also mixes up where some Pokémon can be captured. Take Abra for example, in Blue and Red you can grab the little psychic creature on Route 24 in the grass just north of Cerulean City. In Yellow, however, you have to go south of Cerulean to grab it from Route 5. These are only small changes but it’s enough to make your quest to catch ‘em all a little bit trickier.
Some Pokémon in Yellow can learn moves that they could not in Blue and Red. For example, Charizard can learn Fly in Yellow to fit more in-line with the anime. Pikachu can also learn Surf, but only when linked up to Pokémon Colosseum. Some in-game trades with NPCs also had the Pokémon on offer and desired changed, too.