Each of the fifteen chapters in Ender’s Game opens with a conversation in which Ender’s progress is discussed. Most of the discussions are between two unnamed individuals, who are eventually revealed to be Ender’s instructors, Colonel Graff and Major Anderson.

Ender's Game begins in an elementary school on Earth, where a six-year-old boy named Ender is having an electronic monitoring device removed from his body. This monitor, which allows government officials to evaluate his suitability for military duty, has always marked Ender out as different from the other children, and he wonders whether, without it, he may now be viewed as normal by his classmates and be able to get on better with his older brother Peter—though he has his doubts about this. The removal is painful and Ender is disoriented when he returns to class, though he still finds the lesson on multiplication absurdly simple.

Ender is a third child. This is rare in his society, as parents need special authorization from the government to have more than two children. Ender’s family, the Wiggins, have received this permission in part because their children are so brilliantly intelligent. Other children at school bully Ender and call him a “Third,” and on the day when he has his monitor removed, Ender is bullied by a bigger boy named Stilson. When they fight, the unassuming Ender kicks Stilson hard and seriously hurts him, astonishing Stilson’s friends.

Ender is also bullied at home by his elder brother, Peter, who is ten. They play war games, one of which is called “Astronauts and Buggers.” Peter insists that Ender play a Bugger, since the Buggers never win. He pushes Ender to the floor and threatens to kill him, saying that he could escape punishment by pretending it was an accident. Their sister, Valentine, quickly intervenes, saying she would expose Peter’s lies. Later that night, Peter quite uncharacteristically says he loves Ender and is sorry for the pain caused by the removal of the monitor.

The next day, Ender’s family receives a visit from Colonel Hyrum Graff, director of the prestigious Battle School. Graff informs Ender that Stilson was seriously injured in their fight and asks why Ender beat him so savagely. Ender replies that he was simply thinking ahead and wanted to discourage Stilson from ever challenging him again. After hearing his reasoning, Graff announces that Ender has shown the potential to be a leader and offers him a place at Battle School, an institution that trains gifted children for military roles. Attending Battle School will mean leaving both Ender’s family and the planet Earth, as the school is situated in outer space. Ender is initially reluctant, but Graff persuades him, saying that his skills will be needed in mankind’s war against the Buggers, an advanced alien race that almost wiped out humanity in a previous war. Ender says goodbye to his family but is only really sorry to leave his sister, Valentine, whom he loves devotedly.

En route to Battle School, Ender goes through zero gravity training in a space shuttle filled with other young recruits. Ender quickly realizes that Graff is manipulating the children to make them fight, and Graff explains that he does this to render them more aggressive and effective soldiers. At Battle School, Ender attends classes in mathematics, history, and other subjects relevant to the military positions Battle School students are expected to assume. In their free time, the students are encouraged to play strategy-based arcade games. Ender befriends two boys called Shen and Alai, and a boy called Bernard, who is initially a bully. 

The main activity at the school is the Battle Room, where students are assigned to armies and participate in war games using laser weapons in a zero-gravity environment. Though he’s still a new recruit, Ender is promoted early to the Salamander Army, commanded by an older boy called Bonzo Madrid. Ender disagrees with many of the decisions Bonzo makes as a commander, and Bonzo resents having the younger boy assigned to his army, refusing to train him or let him participate in battles. Ender befriends Petra, a fellow Salamander soldier and one of the only girls in Battle School, and Petra helps Ender improve his battle skills. Over time, the tension between Bonzo and Ender increases, and after Ender disobeys an order during battle (successfully turning what would have been a defeat by the Leopard Army into a draw), Bonzo transfers him to the Rat Army. Ender also clashes with his new Rat Army commander, Rose, but finds continued success in the Battle Room, coming to realize that he has the instincts of a killer—just like his elder brother, Peter.

Back on Earth and two years after Ender has left his family, Peter tells Valentine that though they are only children, he believes they can leverage their intelligence and writing abilities to influence global politics. He wants to focus on the struggles between terrestrial nations, rather than humanity’s war against the Buggers. The two begin to compose anonymous political articles, concealing their identities as children, and circulate them online. They engage in online debates, with Peter, writing under the name “Locke,” putting forth the case for global peace and Valentine agitating for war with Russia under the name “Demosthenes.” Both invented figures soon achieve a high public profile.

At Battle School, Ender has enjoyed great success and, despite his youth, is quickly given command of his own army: Dragon Army. Colonel Graff and Major Anderson challenge Ender with increasingly difficult and unfair Battle Room scenarios, and Ender responds with brilliant originality—but also with ruthless brutality. Bonzo, jealous of Ender’s success, attempts to corner Ender and fight him, an encounter that leaves Bonzo fatally wounded. 

Soon after the incident with Bonzo, Graff promotes Ender to Command School on the distant planet of Eros. There he meets the most famous warrior in the world, Mazer Rackham, who cleverly defeated the Bugger fleet in the previous war by killing their Queen. Mazer becomes Ender’s strategy instructor and explains that he has designed a series of difficult computer-simulated battles, which Ender must complete in order to hone his command skills and one day command the real human fleet against the Buggers.

The battle simulations become increasingly more complex and challenging, pushing Ender to the limits of his endurance. The final simulation—and the test that will determine whether Ender is ready to take command of the fleet—is observed by a number of high-ranking political leaders and military personnel. The simulation takes place at the Bugger’s home planet, which is defended by a vast armada of Bugger ships. Frustrated by the impossibility of defeating such a force with his much smaller fleet but determined to win at any cost, Ender makes the risky decision to sacrifice most of his own fleet in order to shoot a powerful missile directly at the planet, destroying not only the Bugger fleet, but their home world as well.

The room erupts in cheers and applause when the simulation ends, and Ender is shocked to learn that he was commanding the real human fleet and that his trainings have not been simulations, but real battles, which have taken place as the human fleet approached the Bugger’s home planet. Ender’s decision to destroy the planet has, therefore, wiped out the Bugger species entirely. Ender is horrified and accuses Graff and Mazer of tricking him into becoming a mass-murderer. His teachers don't deny it and justify this deception by saying that Ender could have never made the sacrifices and decisions necessary for victory if he had known the battles were real.

Soon after Ender’s defeat of the Buggers, war breaks out on Earth; however, world peace is eventually achieved under the guidance of Locke and Demonsthenes. Ender is made an admiral, though he realizes he can never return to Earth, for Peter, now a political leader, would undoubtedly try to exploit Ender’s fame and influence. Graff is court-martialed for his treatment of the children in the Battle School, but he is promptly acquitted, as his actions are deemed to have been necessary for humanity’s survival.

A year after his victory over the Buggers, Ender is still on Eros, which is receiving an increasing number of visitors from Earth. One of these is his sister, Valentine. She tells him that both she and Peter have become powerful through their Locke and Demosthenes personae and that they have used this influence to have Ender appointed governor of a new human colony in the Bugger galaxy. Ender agrees to this, and he sets off with Valentine on a two-year journey to reach this galaxy. During this time, Valentine writes a history of the wars between humans and Buggers.

Life at the colony is simpler, and Ender becomes a popular and successful governor. One day, while exploring the planet, he discovers the pupa of the last surviving Bugger Queen and finds he is able to communicate telepathically with her. From her, Ender learns that the Buggers did not realize that humans were intelligent life forms in their initial encounter and that they never intended to attack the humans again once they realized their mistake. The Queen asks him to help her colonize a new world for the Buggers. Ender agrees to help her, and the story ends with him taking the pupa of the Queen on a journey to find a new home for her species to live in peace. In this way, Ender hopes to atone for his role in the genocide.