The series features a recurring cast of friends, rivals, and family members:

: A jokester friend who often delivers punchlines.

: Nate’s best friend and the "voice of reason."

: Nate’s single, middle-aged father who refuses to let Nate get a dog. The Evolution of the Franchise Big Nate, Small Screen: An Interview with Lincoln Peirce

Nate is an 11-and-a-half-year-old "C-grade student" who believes he is destined for greatness, despite holding the school record for the most detentions.

: Nate’s long-time crush, though his feelings are famously unrequited.