"Big Nate" follows the adventures and misadventures of Nate Wright, a rebellious yet spirited male sixth-grader, along with his fellow classmates and teachers. He is portrayed as a boy with very little interest in studies or conforming to standards, which has led him into several conflicts with his social studies teacher Mrs. Godfrey, whom he considers to be his nemesis. Strips also focus on Nate's home life and friendships with his best friends Francis and Teddy. Answering questions from fans in the Washington Post, Peirce revealed the following about the creation of the strip:
"Big Nate started out as more of a 'domestic humor' strip than it is now. It was my intention to feature a lot of stories about Nate's single dad, and all the comic possibilities inherent in that. But before too long, I realized that the part of the strip that I enjoyed most was the school humor. I'd been a teacher myself, and schools can be very funny places."
Big Nate has been running from January 7, 1991, to December 31, 2017 before going into hiatus which ended in July 16, 2018.
The series takes place in a fictional town called Rackleff which is located in Maine, despite there being a street called Rackleff which is in Maine and a senior community called that in Canby, Oregon.
When it comes to the title of each Big Nate book, every comic collection has the word “big” lowercase while actual novels have “BIG” uppercase.
Almost all Big Nate books have Jeff Kinney's quote, "Big Nate is funny, big time.", on the top of the front cover.
"Big Nate" is named after the author's older brother, Johnathan. He realized the name had the name "Nathan" within it, and soon after, he started calling him "Big Nate".
The comic strip went on a brief hiatus from December 31th, 2017 to July 15th, 2018.