The battle against Greed and his group continues, with the state military and Führer King Bradley himself now joining in. As Ed and Al begin to wonder about Bradley's true motive for getting involved, Greed is taken to the homunculus' secret underground lair so his fate can be decided.

Scar and Yoki gain a new companion in the form of a young girl from Xing named Mei Chan, who displays her country's unique form of alchemy. Lieutenant Riza Hawkeye recruits an unlikely new ally for Colonel Roy Mustang, whilst Edward and Alphonse return to Rush Valley to get Edward's automail arm, but the brothers encounter Ling Yao from Xing, and his two dangerous bodyguards.

Ed, Al and Winry arrive in Central to continue their research, and discover the truth about what happened to Lt. Colonel Hughes. Meanwhile, as Colonel Mustang continues to search for clues regarding Hughes' murderer, Second Lieutenant Maria Ross is accused of committing the crime.

After being interrogated, Second Lieutenant Maria Ross is convicted for the murder of Brigadier General Hughes. Upon hearing about the news, Barry the Chopper sets out to break her out of jail. Meanwhile, Major Armstrong takes Ed with him on a trip under the pretext of going to Risembool to get his automail repaired.

Edward travels with Armstrong and Breda to an unexpected place, where he learns the truth of what happened to Maria Ross. Back in Central, Ling visits Alphonse and Winry to apprise them of the events, while a new foe appears to cause trouble for Mustang's subordinates. Elsewhere, Ed encounters some people who reveal horrifying details concerning the fate of Winry's parents.

Alphonse joins up with Mustang and his subordinates as they follow after Barry's original body. The chase leads them to the Third Laboratory, where Barry infiltrates, and they take the opportunity to begin a thorough search of the laboratory. Unbeknownst to them, Lust doesn't intend for any of them to make it out alive.

As Edward returns to Resembool, he surprisingly sees his father, Hohenheim, in front of his mother's grave. That night, Ed hears a startling conversation between his father and Pinako. The next day, Hohenheim gives Pinako a grim warning about the future, and Ed goes to the place where his home once stood, looking for a source of new hope.

Edward and Alphonse meet with Mustang at the hospital, where they look over the events that occurred in the Third Laboratory, and they realize that the Homunculi's hideout may signify just how high up the level of corruption in the military is. Scar returns to Central to begin his killing spree anew, and the brothers come up with a dangerous plan to both confront Scar and lure the Homunculi out of hiding. Ling and Lan Fan hear of their intentions and eagerly agree to assist them, but are soon faced with a situation that threatens their survival.

While Ling tries to find a way to escape from Wrath, Edward and Alphonse battle against Scar. Winry hears about the brothers' predicament and manages to find her way to them, but she soon learns the truth surrounding her parents' deaths, and from that knowledge, she struggles to decide if she should continue the cycle of hatred.

Ed leaves Winry in the custody of the military to catch up with Al. Meanwhile, as Bradley continues to chase after Ling and Lan Fan, Gluttony goes after Scar. As Ed rejoins Al in his fight against Scar, Gluttony arrives on the scene. Ling then joins the fight, and is able to capture Gluttony by using his regenerative ability against him. Lan Fan manages to escape Bradley by cutting off her disabled arm to throw off her blood trail. Riza arrives and drives off with Ling and Gluttony, keeping it secret from the military. As Ed and Al are about to apprehend Scar, they are stopped by May Chang, who uses her alchemy to escape with him. However, Ed and Al manage to take custody of her panda, Xiao Mei. As they arrive back at HQ, they tell Winry everything. She feels depressed, believing all she can do is wait, but feels better when she receives a call from her customers back in Rush Valley. As she goes on the train back, Winry thinks she may be in love with Ed. Ed and Al later join up with the others at a hideout, where Lan Fan's wounds are treated. Ling reveals to Ed, Al and Roy that Bradley is a Homunculus. When Gluttony hears mention of Roy, the one who killed Lust, he transforms and blows the corner off the hideout.

Dr Marco is in the custody of the homunculi, and has to cooperate in exchange for his village's safety. Meanwhile, Ed, Al and Roy try to escape from Gluttony, who has become able to swallow anything in his sights. After losing him, Roy and the others leave to safety whilst Ed, Al and Lin stay to fight. Envy arrives to stop Gluttony from harming Ed and Al. Hearing this, Ed and Al face Gluttony whilst Lin faces against Envy. After some struggles on both ends, Gluttony ends up accidentally swallowing Ed, Lin and Envy. Roy goes to a meeting and ends up confronting Bradley and realizing what Hughes meant. Ed wakes up in a strange room, covered in blood.

Ed and Lin find themselves in a dark place, realizing they're inside Gluttony's stomach, and try to find a way out. May is worried about Xiao Mei, explaining to Yoki about their circumstances, so Scar decides to help search for her. Ed and Lin are approached by Envy, who explains that Gluttony was a failed attempt at recreating the Door of Truth and there is no exit. Envy also reveals he was the one who started the Ishbalan war, before transforming into a giant beast. Meanwhile, Al gets Gluttony to take him to Father, who is apparently in Central, and Bradley gets leverage over Roy by transferring his men to various headquarters and assigning Riza as his personal assistant, effectively making her his hostage.

Ed and Lin face off against Envy, and Ed finds himself hesitating to attack due to all the people embedded into Envy's body and gets swallowed. Meanwhile, Scar and May find Shao May with Al and Gluttony and decide to follow them down to an underground tunnel, fighting off several chimeras. Ed spots the Philosopher's Stone inside Envy and manages to figure out a way to escape from Gluttony after seeing the missing piece from the ruins of Xerxes. Bradley explains to Roy how he was trained from birth for leadership and was injected with the Philosopher's Stone. Using various pieces of the Xerxes ruins found in Gluttony's stomach, Ed reluctantly uses the souls inside Envy's stone to transmute himself and open the Door of Truth to escape through. Ed finds Al's body but is unable to bring it back since it isn't his. However, before the Door closes, he bursts through yelling to Al's body that he will come back to get him someday.