Matthew Holm was born and raised in the suburbs of Philadelphia, Pa., and has been drawing comics since he was in middle school. Growing up reading four older siblings' comic books and comic strip collections (including Peanuts, Calvin and Hobbes, and Bloom County), he hoped he might one day grow up to draw a daily newspaper comic strip. He mentored under Pulitzer-prize-winning editorial cartoonist Tony Auth while in high school, and in college, while studying English and Art at Penn State, he drew weekly editorial cartoons for the school newspaper. After college, he worked in New York City as a writer and editor for Hearst's Country Living Magazine, and drew a daily web comic (before the term "web comic" really existed) in his spare time.

He first began working with his sister, Jennifer, as a copy editor and fact-checker for her Boston Jane novels, and later drew several pages of comics for her book Middle School Is Worse than Meatloaf. When Jenni came to him in 2001 with the idea of making a comic book with a female heroine named Babymouse, he again picked up his pen and the two worked out the ideas and look for what became one of the first graphic novel series written specifically for children. Today, he continues to collaborate with his sister on several graphic novels each year, both for the Babymouse series as well as the Squish series. He currently lives in Portland, Ore., with his wife and dog.