Hiro Hamada is a 14-year-old robotics genius in the futuristic fictional city of San Fransokyo. Having graduated high school at 13, he now spends his time participating in illegal bot fights. To redirect Hiro, his elder brother Tadashi takes him to his robotics lab at the San Fransokyo Institute of Technology, where Hiro meets Tadashi’s friends, GoGo, Wasabi, Honey Lemon, and Fred, as well as Baymax, the inflatable healthcare robot Tadashi created. Hiro also meets Professor Callaghan, the head of the university’s robotics program. Amazed, Hiro decides to apply to the university. To enroll, he signs up for the school’s science fair and presents his project: microbots, swarms of tiny robots that can link together in any arrangement imaginable using a neuro-cranial transmitter. Impressed, Professor Callaghan grants Hiro acceptance. When a fire breaks out at the university, Tadashi rushes in to rescue Callaghan. An explosion apparently kills both Tadashi and Callaghan.
Weeks later, a depressed Hiro inadvertently activates Baymax again, who follows Hiro’s only remaining microbot to an abandoned warehouse. There, the two discover that someone has been mass-producing the microbots, and are attacked by a man wearing a Kabuki mask, who is controlling the bots. After they escape, Hiro equips Baymax with armor and a battle chip containing various karate moves, and they track the masked man to the docks. GoGo, Wasabi, Honey Lemon, and Fred arrive, and the masked man attacks the group. The six escape to Fred’s mansion, where they decide to form a superhero team to combat the man.
The group tracks the masked man, who they suspect to be Alistair Krei, president of Krei Tech, to an abandoned Krei Tech laboratory, which they find was researching teleportation technology until a test pilot was lost in an accident. The masked man attacks, but the group manages to knock off his mask, revealing him to be Professor Callaghan, who had stolen Hiro’s microbots to shield himself from the explosion. Realizing that Tadashi had died for nothing, Hiro, enraged, removes Baymax’s personality chip, leaving only the battle chip, and orders him to kill Callaghan. Honey re-installs the healthcare chip at the last second, preventing Baymax from carrying out the kill order. Callaghan escapes, and Hiro, furious at his friends’ intervention, leaves. Back home, Hiro tries to remove the healthcare chip again, but Baymax prevents him, stating that vengeance is not what Tadashi would have wanted. To comfort him, Baymax shows Hiro videos of Tadashi running numerous tests during Baymax’s development. A remorseful Hiro apologizes to his friends, and the team reunites to stop Callaghan.
The group discovers that Krei’s test pilot was Callaghan’s daughter Abigail, and that Callaghan is seeking revenge on Krei. Callaghan interrupts a public Krei event and attempts to destroy his headquarters using Krei’s teleportation portal. The team saves Krei, but the portal remains active. Baymax detects Abigail inside, alive but in hyper-sleep, and leaps into the portal with Hiro to rescue her. They find Abigail’s pod, but Baymax is damaged by debris. Knowing that the portal will collapse, Baymax uses his armor’s rocket fist to propel Hiro and Abigail back through the portal, forcing them to leave him behind. Callaghan is arrested. Sometime later, Hiro discovers Baymax’s personality chip clenched in the rocket fist. He rebuilds Baymax and the six friends continue their exploits through the city, 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, where a building has been 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, a retired superhero, arrives stating “We have a lot to talk about” as they embrace each other.