Steps
Beat the Elite Four. You cannot get Mewtwo until you defeat the Elite Four and become the Pokémon champion, you can catch Mewtwo after fulfilling the quest in One Island..
Obtain the National Pokedex from Professor Oak. You will need to have captured sixty Pokémon before he will give it to you.
Fix the Network Machine by finding the Ruby and Sapphire (see below). If you are playing Red, Blue, Yellow, Gold, Silver, or HeartGold, SoulSilver, then you can go directly to the cave in Cerulean City.
Get the Ruby
Go to Island 1. You will need a Pokémon who knows Surf to do this. Speak to Celio and he will explain that you need to find an item for his machine.
Go to the entrance of Mt. Ember. On the lower right side of the area, you will see some Team Rocket members. You will hear the first password to the Rocket Warehouse. Battle them, and enter the cave.
Proceed all the way down to the bottom level. You do not need to read any of the braille charts. You will need a Pokémon with Strength to get through the cave.
Pick up the Ruby and exit. You can either use an escape rope, use "Dig" or exit the way you came in.
Get the Sapphire
Go to Island 6 and find the Dotted Hole, which can be seen on the Town Map. At the entrance, read the braille sign. It will say "Cut," so you make sure you bring a Pokémon who knows Cut. If you have not yet saved Lorelei from Island 4, a scientist will be blocking the way.
Inside the cave, look at the braille signs. They will tell you which hole to fall down. If it has 2 symbols, it means go up. If it has 5, then it's right. If it has 4, then it is either left or down. If you mess up, you will have to start over again.
On the bottom level, you will see the Sapphire. Don't get too excited; a super nerd will take it first. He will then give you the second password for the Rocket Warehouse.
Go to the Rocket Warehouse, found on Island 5. You will need to defeat all the Team Rocket members to get to the boss.
In the final room, you will find the super nerd who stole the Sapphire. Battle him. When you beat him, you will get the Sapphire.
Travel to Island 1. Give the gems to Celio, the man who operates the machine on the island. He will connect the regions of Kanto and Hoenn by signal and open up the way to Mewtwo.
Finding Mewtwo
Go to Cerulean City. At the top left corner of the town, you will see a cave that is now open. Travel north to Route 24 and use a Pokémon to Surf to the entrance.
Inside the cave, you will need to navigate the maze to the bottom floor. Make sure your Pokémon team is at a high level; there are a lot of strong Pokémon here (levels 46-70).
At the end, you will see Mewtwo. Save your game before battling him, as this is your only chance to catch him and he is very powerful. See the Tips section for some methods of catching Mewtwo. You should bring at least 50 Ultra Balls. Eric Mylonas Eric Mylonas, Gaming Strategy Expert When facing the genetically engineered Pokémon Mewtwo, preparation is key. Come equipped with plenty of Ultra Balls and healing items to withstand its devastating psychic attacks. Lower its HP significantly while inflicting status conditions like paralysis or sleep to stop it from recovering. Even for experienced trainers, catching this powerful legendary will require skill, strategy, and a bit of luck.
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