Hiro Hamada is a 14-year-old robotics genius who lives in the futuristic city of San Fransokyo, and spends his time participating in back-alley robot fights. His older brother, Tadashi, worried that Hiro is wasting his potential, takes him to the robotics lab at his university, where Hiro meets Tadashi's friends, GoGo Tomago, Wasabi, Honey Lemon, and Fred, as well as Baymax, a personal healthcare companion Tadashi created. Amazed, Hiro decides to apply to the school. He presents his project—microbots, swarms of tiny robots that can link together in any arrangement imaginable—at an annual exhibition to gain admission. Professor Callaghan, the head of the program, is impressed, and Hiro gets in. When a fire breaks out at the university, Tadashi rushes in to rescue Callaghan but the building explodes and both are killed. As a result of losing his brother, Hiro secludes himself from others.
One day, Hiro accidentally activates Baymax. Baymax follows one of Hiro's microbots to an abandoned warehouse, where he and Hiro discover that someone has been mass-producing Hiro's bots; they are attacked by a masked man called Yokai, who is controlling the bots. Realizing this man has stolen his project, Hiro decides to catch him and upgrades Baymax with armor and a battle chip containing various karate moves. After Yokai attacks Hiro, Baymax, GoGo, Wasabi, Honey, and Fred in a Mitsubishi Minica Toppo, the six form a superhero team.
The group discovers that a former lab of Krei Tech, a prestigious robotics company, was experimenting with teleportation technology. The test went awry when the human test pilot vanished inside an unstable portal. Yokai is revealed to be Professor Callaghan, who explains that he stole Hiro's bots and used them to escape the fire, but he did not had any guilt or regret about Tadashi's death. Realizing that Tadashi died in vain, Hiro angrily removes Baymax's healthcare chip, leaving him with only the battle chip, and orders him to kill Callaghan. Baymax loses all of his softness, and develops a threatening, evil aura. The team (other than Hiro) tries to stop Baymax with no success. Baymax almost kills Callaghan until Honey manages to insert the healthcare chip back in.
Angry at his friends, Hiro goes home but breaks down when Baymax asks him if killing Callaghan will make him feel better. To soften Hiro's loss, Baymax plays humorous clips of Tadashi's running tests on him during Baymax's development. Hiro realizes that killing Callaghan is not what Tadashi would have wanted and makes amends with his friends.
The group discovers that the test pilot was Callaghan's daughter Abigail; Callaghan is seeking revenge on Alistair Krei, the president of Krei Tech, whom he blames for her death. They save Krei and destroy the microbots, but the portal remains active. Baymax detects Abigail from inside the portal and he and Hiro rush in to save her. On their way out, Baymax's armor is damaged and he realizes the only way to save Hiro and Abigail is to propel them through with his rocket fist. Hiro refuses to leave him, but Baymax insists until Hiro tearfully gives in. Hiro and Abigail make it back, and Callaghan is arrested.
Sometime later, Hiro discovers Baymax's healthcare chip, which contains his entire personality, clenched in his rocket fist. Delighted, Hiro rebuilds Baymax and they happily reunite. The six friends continue their exploits through the city, staying unknown, and fulfilling Tadashi's dream of helping those in need.
During the end credits, it is shown through newspaper headlines that Hiro has been awarded a grant from the university and a building is dedicated to Tadashi. In a post-credits scene, Fred accidentally opens a secret door in his family mansion and finds superhero gear inside. His father, who turns out to be Stan Lee, arrives and embraces him, stating that they have a lot to talk about.
