In the very near future, a race of huge, insect-like aliens is discovered traveling the galaxy. These aliens, which are known as the Uchuu Kaijuu, or Space Monsters (Note: This name is what they are referred to throughout the series, although the Super Robot Wars games names them the "STMC" or "Space Terrible Monster Crowd"), seem dedicated to the eradication of the human species as the latter takes its first steps away from the solar system, and they are getting closer and closer to Earth. Humanity has responded by developing spacegoing battleships and giant fighting robots. These complex robots – RX-7 Machine Weapons – are actually an advanced type of fighting suit, piloted by a single occupant. As advanced as they are, however, they are being used as trainers for a new weapon, the Gunbuster. However, being relatively new technology, they are difficult to operate (stock shots show pilots working multiple controls with hands and feet, while fingers rapidly operate switches on the handgrips), so pilot candidates are selected from the best and brightest youth on Earth and the Lunar colony. These are trained at schools around the world.
The story begins in the year 2023, not long after the first battles with the aliens, and centers on young Noriko Takaya (??????? Takaya Noriko) (voice: Noriko Hidaka). Although Noriko's father was a famous admiral in the space fleet who went missing following one of the first battles of the war, her own talents as a pilot are questionable – especially when compared to the other students. Nonetheless, she has entered a training school on Okinawa, largely due to the influence of her instructor, "Coach Ohta," who was one of Admiral Takaya's crew. He has faith that she will overcome her early clumsiness, while other students are critical of her inability.
Noriko idolizes the beautiful, competent and talented Kazumi Amano (??????? Amano Kazumi) (voice: Rei Sakuma). She is not alone, the other students recognize that Amano is the top RX-7 pilot at the school, and likely the entire world. Coach Ohta shows the extra training which Amano creates for herself, inspiring Noriko to look within herself for strengths which she didn't know that she had.
Only two Gunbuster pilots from each school will be selected for the real mission. Amano, of course, will be going, and all of the others want the second slot on the team. Takaya is determined to win, not only to be with Amano but also to find (or avenge) her father. She is thrilled to discover that she has in fact been chosen as the second Japanese pilot.
Following that selection, conflict between Takaya and other students comes to a head, when the second-best RX-7 pilot at the school publicly challenges her to a one-on-one fight. Planned for late at night, when none of the school authorities will be around to stop it, Ohta learns of the duel and comes to the battleground – but does nothing. He is there to observe, and perhaps to save Takaya's life, if the combat gets too intensive.
Takaya is on the defensive from the start, and the older student humiliates her by action and over the radio. As Takaya's RX-7 is pummelled, Noriko realizes that her difficulties are a case of sensory overload – she is getting too much information from the electronic monitoring systems. She turns off her monitors, but as the systems go dark, her opponent is infuriated by the perceived insult and prepares the final, killing blow. Just as it appears that Noriko is doomed, she destroys her opponent's RX-7 with a "Thunder Kick." Her opponent muses that the school rookie has beat her with an advanced maneuver which she hadn't been taught. This is the proof that Ohta was seeking, that Noriko had an innate ability which would be invaluable in the battles to come.
Together, with Coach Ohta and friends to come, Noriko and Amano face the trauma of war and the discovery of loss.
For the final battle, Earth has created Buster Machine III, a giant bomb. When detonated this will cause a black hole to be formed that will suck the space monsters in.
Nel futuro prossimo, una razza di alieni giganteschi dalle sembianze biologiche (a metà fra vegetali ed insetti) viene individuata pericolosamente vicino al Sistema solare. Nel monitorare i loro progressi, gli umani intuiscono che la loro intenzione è quella di distruggere la razza umana esattamente come il sistema immunitario si disfa dei batteri nocivi; l'intuizione viene confermata dall'aggressività degli alieni, dalla distruzione di una stella simile al Sole (sfruttata dagli alieni come nido di cova) e dal loro progressivo avvicinarsi al pianeta Terra. L'umanità è quindi costretta a rispondere con l'attacco. Per l'occasione, vengono coinvolte tutte le risorse terrestri al fine di creare una flotta di astronavi da combattimento e dei robot guerrieri giganti. Questi ultimi saranno pilotati dai migliori adolescenti del pianeta, convocati dalle apposite scuole di allenamento sparse per tutto il mondo.
La storia comincia nell'anno 2015, non molto dopo la prima battaglia contro gli alieni, e si concentra sulle vicende della giovane Noriko Takaya (??? ???, Takaya Noriko?). Il padre di Noriko, deceduto sotto il fuoco avversario, fu uno dei principali ammiragli della flotta spaziale responsabile del successo ottenuto contro i primi attacchi nemici. Durante la serie, grazie all'aiuto dei suoi compagni tra cui la bella e talentuosa Kazumi Amano (??? ???, Amano Kazumi?), Noriko subirà una sensibile crescita psicologica e combatterà contro i dolori della guerra, l'incomunicabilità tra persone e la sua stessa mancanza di autostima.