Felt and Viese, alchemists-in-training on the floating continent of Eden, are the game's main characters. Viese becomes a full-fledged alchemist, and when she finds Felt at the Belkhyde Gate (a sealed gateway to another world), they go to a forest so Viese can make a pact with an elemental spirit. They find the Azure Azoth, an Excaliber-like sword, and Felt succeeds in pulling it out.

He hears a voice telling him he must go to Belkhyde (which has been unsealed by the Azure Azoth) because Eden is in turmoil. After parting from Viese, he staggers across the Tatalian desert before collapsing and being found by Noin. Noin claims to be part of the Simsilt, an army fighting to liberate Belkhyde from the Empire. Felt and Noin rescue Max, leader of the Simsilt, from the Riesevelt lighthouse and move to Agito Cove (Simsilt's base). Felt and Viese learn about the Share Ring, which allows a user to send items to another. Hagel (the blacksmith) is recruited, and they are rescued by the dragon man Gray. Felt returns to Agito, travels to the eastern continent and sees the sea for the first time.

During the journey to Altena Church, Felt finds the girl who tried to kill him poisoned in a forest. After bringing her to Max's Camp, Viese develops a cure for Fungo's poison. Felt and the others go to Altena Church and are stopped by Chaos, who defeats Felt and Fee and is chased by Gray. When they reach Altena Church, the purposes of the Azoths, Eden and the Gardo Continental Drive are revealed. When Viese finds a map of workshops scattered across Belkhyde, this becomes the focus of the rest of the game.

Felt looks for Chaos, who was not present at the battle. He finds an Altena Nun on the bridge leading to the western continent who tells him that Chaos arrived at Altena Church. When Felt arrives, he finds Mother Eizlen frozen by the Crimson Azoth's spell (which killed Max earlier). Felt fights Chaos in the lower levels of Altena Church (where the Gardo Continental Drive is stored), and is fossilized with the Exzanosis spell. Viese begins to worry about Felt, and follows him to Belkhyde.

After the restoration of the Azure Azoth, Felt dissipates the mist which Palaxius spread over Eden. After chasing him to the Temple of Creation, Felt and his friends learn about Iris (the reincarnation of Lilith) and defeat Palaxius. Iris is freed, and everyone finds a place in the world.

Atelier Iris 2: The Azoth of Destiny created by