After Edward Elric recovers his arm and leg and his brother Alphonse’s body, Edward is dragged from his homeworld through the Gate of Alchemy—the source of alchemical energy—to a parallel world of Earth in 1923. The world is fundamentally governed by the laws of modern science instead of alchemy. When Edward arrives there, he discovers that he has been stripped of his alchemical powers and his newly restored arm and leg.
Two years later, in Munich, Germany, Edward researches rocketry with his friend Alfons Heiderich, a young man who resembles Alphonse, in the hopes of returning to his world. Edward rescues a troubled, persecuted Romani woman named Noah from being sold. Noah is taken in by Edward to live with him and Alfons, and begins having visions concerning Edward’s life in his world. The next day, Edward meets Fritz Lang, a Jewish film director resembling King Bradley, who persuades Edward into helping him hunt down a dragon he has been seeking for inspiration for his next film. The dragon, which turns out to be homunculus Envy, attacks Edward, but is then weakened and captured by members of the Thule Society.
The Thule Society, led by Karl Haushofer and Dietlinde Eckhart, use Envy and Edward’s kidnapped father Hohenheim as catalysts to open a portal to Edward’s world, believing it to be the utopia Shamballa after learning about it from Hohenheim. A number of armored soldiers are sent through the portal, only to emerge on the other side in the city of Liore as mutated zombie-like creatures. Alphonse, who had come to visit Liore, fights off the armored soldiers and merges parts of his soul to three of their suits to aid him in combat. Meanwhile, Edward breaks into the Thule Society headquarters and accidentally reopens the portal, returning the dead armored soldiers to Earth and allowing Alphonse’s armored form to briefly reunite with his brother before his soul returns to his body, increasing Edward’s determination to return to his world.
Alphonse is guided by the homunculus Wrath to the underground city beneath Amestris’ Central City to reopen the Gate of Alchemy. There, they are attacked by the homunculus Gluttony, who fights and mortally wounds Wrath. At Wrath’s insistence, Alphonse transmutes and sacrifices the two homunculi to use as material to open the Gate. Meanwhile, in Munich, the Thule Society persuades Noah into guiding them on how to correctly open the Gate based on what she had learned from reading Edward’s mind. Edward learns from Lang that the Thule Society plans to use the weapons from his world to help Adolf Hitler in his attempt to start a revolution, and heads to stop them. Hohenheim and Envy are both transmuted at the same time that Alphonse transmutes Gluttony and Wrath. With the Gate opened, Eckhart leads a fleet into the other world, where she gains the ability to use alchemy. However, she begins to go mad with power and fear of her new surroundings and launches an attack on Central City. Alfons launches Edward in a rocket-powered plane to return him to his world before being gunned down.
Edward appears in his world, reunited with Alphonse and their friend Winry Rockbell, who fits Edward with new automail limbs. The Amestris military manages to stop most of Eckhart’s soldiers with the help of Roy Mustang. Edward battles Eckhart before Alphonse transmutes parts of his soul to a group of armors, which attack her and force her to retreat. Upon reappearing in her own world, Eckhart is covered with shadow creatures from the Gate and killed by an officer out of alarm of her new, monstrous appearance. Understanding the danger posed by the connection between the two worlds, Edward returns to Earth to seal the Gate on that side, knowing he will be trapped on Earth forever. Instead of sealing the Gate on the other world’s side as per Edward’s request, however, Alphonse has Mustang seal the Gate and follows Edward to remain with his brother. Following Alfons’ funeral, the Elric brothers leave Munich with Noah, intending to destroy the weapons meant to be used in Hitler’s attack and enjoy their new lives together on Earth.