In an alchemical ritual gone wrong, Edward Elric lost his arm and his leg, and his brother Alphonse became nothing but a soul in a suit of armor. Equipped with mechanical ""auto-mail"" limbs, Edward becomes a state alchemist, seeking the one thing that can restore his and his brother's bodies...the legendary Philosopher's Stone.

The story enters its final stretch as the Elric brothers learn of the homunculi's ultimate plan to turn all of Amestris into an alchemical bloodbath on the "Day of Reckoning." While tempted to use the open portal that day to get their bodies back, for now the brothers build opposition to the homunculi-corrupted military with others who have learned of the grisly plan. While Al learns the secret of the homunculi's origins from his father, Ed joins forces with a familiar homunculus who seems to be having pangs of conscience.