In the futuristic city of San Fransokyo, young robotics prodigy Hiro Hamada spends his time participating in illegal robot fights until his older brother, Tadashi, directs his talents toward a more productive pursuit. Tadashi introduces Hiro to his university's robotics lab, where Hiro meets Tadashi's friends and Baymax, an inflatable healthcare companion robot Tadashi created. Inspired by the lab's innovative atmosphere and its occupants' projects, Hiro decides to apply for the university. To impress the program's professor and earn his place, Hiro develops a groundbreaking invention called microbots, a swarm of tiny robots he can telepathically control through a neural-cranial transmitter.

Tragedy strikes on the night of Hiro's triumphant presentation, as a fire breaks out at the expo center, leading to a series of events that results in a devastating loss for Hiro. In his grief, he secludes himself, but his life takes an unexpected turn when he accidentally activates Baymax. As Baymax tries to assist Hiro through his emotional pain, they stumble upon a mysterious masked figure controlling Hiro's stolen microbots. Suspecting a deeper conspiracy, Hiro equips Baymax with armor and combat programming, forming an unlikely heroic duo. Joined by Tadashi's friends, who also enhance their own capabilities with technology, they form a team, setting out to uncover the truth behind the masked figure's identity and the tragic event that changed Hiro's life forever.