Shinji Ikari is sent for by his estranged father, Gendo, the Supreme Commander of NERV. As Shinji wanders around the city of Tokyo-3, which has been deserted following an emergency announcement, he is caught in the crossfire between UN forces and the Fourth Angel
. Lt. Colonel Misato Katsuragi rescues Shinji and brings him to Geofront and NERV headquarters. Gendo then pressures Shinji into piloting Evangelion Unit-01 against the Angel, as the other Evangelion pilot, Rei Ayanami, is too injured to do so. Shinji initially refuses out of fear, but upon seeing Rei wrapped in bandages and carried in on a stretcher, he reluctantly agrees.
Shinji pilots Unit-01 and wins the fight after Unit-01 goes berserk
and destroys the Angel. After the fight, Shinji is taken in by Misato as her new housemate and enrolled in the local middle school. Shinji tries to settle in with his newfound life alongside Misato, Rei, and the others while he receives training to defend Tokyo-3 and the world from the coming Angels.
A short time later, the Fifth Angel arrives. Toji Suzuhara and Kensuke Aida, two of Shinji's classmates, sneak out of the emergency shelters to see the action. Shinji enters the battle, and the Angel slams Unit-01 into a mountainside, nearly crushing Toji and Kensuke. Misato has the two take cover in Unit 01's cockpit before ordering Shinji to retreat, but he disobeys and destroys the Fifth Angel with Unit-01's equipped knife. Misato later reprimands Shinji for disobeying her.
Not long after, the Sixth Angel appears and tries to drill into the Geofront. Shinji is ordered to deploy Unit-01 against it, but the Angel fires a particle beam at the Eva, critically injuring Shinji. Shinji wakes up from a coma some time later and is too fearful to pilot again. Seeing that, Rei tells him she will take his place and leaves for the mission alone.
To motivate the despondent Shinji, Misato takes him down to the deepest level of the base and shows him a giant white entity crucified to a gigantic cross-like restraint: the Second Angel, Lilith. Misato explains that reaching this area is the goal of the Angels and that any contact between them and Lilith would bring about Third Impact and the end of all life on Earth.
With this information and encouragement from his new friends at school, Shinji agrees to pilot Unit-01 alongside Rei, who pilots Unit-00 against the Angel. Shinji manages to destroy the Angel by sniping it using an experimental positron rifle, which requires the entire electrical power output of Japan to function. Rei is nearly killed defending Shinji from the Angel's return fire, but he is able to save her by dunking the damaged Unit-00 into water to cool it off and prying her cockpit out using Unit-01's knife. Shinji cries out of fear of nearly losing her, and Rei, normally cold and emotionless, eventually shares a smile with him.
On the surface of the Moon, Kaworu Nagisa awakens from one of the nine coffin-like containers arranged in line on the surface. In a pit in front of him, surrounded by construction equipment and scaffolds, is an unidentified giant, wearing a purple seven-eyed mask and wrapped in white bandages. A black monolith appears before Kaworu, through which he and SEELE 01 engage in a brief, cryptic conversation. Kaworu says that "the third one" has not changed at all and that he looks forward to meeting Shinji.