A new villain, Major Blast, appears in the city and targets Fred.
- Ryan Potter as Hiro Hamada
- Scott Adsit as Baymax
- Génesis Rodríguez as Honey Lemon
- Khary Payton as Wasabi
- Jamie Chung as Go Go Tomago
- Brooks Wheelan as Fred
- Susan Sullivan as Mrs. Frederickson/Major Blast
- Stan Lee as Mr. Frederickson
- John DiMaggio as Roddy Blair
- David Shaughnessy as Heathcliff
- John Michael Higgins as Mini-Max
- Diedrich Bader as Bluff Dunder, Duff Dunder, Cameraman
- Zehra Fazal as Basemax
- Roddy has finished creating an artificial training simulation room for Big Hero 6's secret lair.
- Mrs. Frederickson is revealed to have been aware of her husband's past as Boss Awesome and has known all along that Hiro and his friends were Big Hero 6.
- She also references Phase Three of the "Big Hero-verse", involving more powerful villains and the police turning against them, another major nod to the Marvel Cinematic Universe.
- Mrs. Frederickson's line, "Frederick, I am your mother" when she is unmasked as Major Blast is a reference to how Luke Skywalker learned Darth Vader was his father in Star Wars: The Empire Strikes Back.